WO2005121075A1 - Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals - Google Patents

Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals Download PDF

Info

Publication number
WO2005121075A1
WO2005121075A1 PCT/EP2005/006207 EP2005006207W WO2005121075A1 WO 2005121075 A1 WO2005121075 A1 WO 2005121075A1 EP 2005006207 W EP2005006207 W EP 2005006207W WO 2005121075 A1 WO2005121075 A1 WO 2005121075A1
Authority
WO
WIPO (PCT)
Prior art keywords
halo
conh
unsubstituted
poly
substituted
Prior art date
Application number
PCT/EP2005/006207
Other languages
French (fr)
Inventor
Noëlle GAUVRY
Pierre Ducray
Thomas Goebel
Ronald Kaminsky
Original Assignee
Novartis Ag
Novartis Pharma Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novartis Ag, Novartis Pharma Gmbh filed Critical Novartis Ag
Priority to JP2007526305A priority Critical patent/JP2008501761A/en
Priority to EP05751761A priority patent/EP1758849A1/en
Priority to AU2005251917A priority patent/AU2005251917B2/en
Priority to US11/596,961 priority patent/US7642379B2/en
Publication of WO2005121075A1 publication Critical patent/WO2005121075A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/26—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups, amino groups and singly-bound oxygen atoms bound to the carbon skeleton

Definitions

  • the present invention relates to new amidoacetonit ⁇ ' le compounds of the formula
  • Ar is unsubstituted or one- or poly-substituted aryl or hetaryl
  • R is hydrogen, C C 6 alkyl, halo-CrC 6 alkyl, CrC 6 -alkylcarbonyl, C ⁇ -C 6 alkoxycarbonyl, allyl, C C 6 alkoxymethyl, unsubstituted or one- or poly-substituted phenylcarbonyl, C r C 6 alkylsulfonyl or unsubstituted or one- or poly-substituted phenylsulfonyl;
  • R 2 , R 3 , R 4 , R5 und R 6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted CrC 6 alkyl, unsubstituted or one- or poly-substituted C 2 -C 6 alkenyl, unsubstituted or one- or poly-substituted C 2 -C 6 alkinyl, unsubstituted or one- or poly-substituted CrC 6 alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C ⁇ Cealkoxy and halo-Cr C 6 alkoxy; unsubstituted or one- or poly-substituted C 3 -C 6 cycloalkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen and C C 6 alkyl; or unsubstitute
  • R 7 and R 10 are, independently of each other, NH 2 , OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, unsubstituted or one- or poly- substituted phenylthiocarbamido, unsubstituted or one- or poly-substituted C r C 6 alkylthiocarbamido, unsubstituted or one- or poly-substituted Ct-C ⁇ alkoxythiocarbamido, unsubstituted or one- or poly-substituted phenyloxythiocarbamido, unsubstituted or one- or poly-substituted phenylaminothiocarboxy, unsubstituted or one- or poly-substituted phenyloxythiocarboxy, unsubstituted or one- or poly-substituted phenylamin
  • R 8 is halogen, nitro, cyano, C C 6 alkyl, halo-C C 6 alkyl, d-Cealkoxy, halo-C C 6 alkoxy, C 2 -C 6 alkenyl, halo-C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkoxy, C 3 - C 6 cycloalkylamino, C -C 6 cycloalkylthio, C 2 -C 6 alkenyloxy, halo-C 2 -C 6 alkenyloxy, C C 6 alkylthio, halo-CrC 6 alkylthio, C C 6 alkylsulfonyloxy, halo-C C 6 alkylsulfonyloxy, C C 6 alkylsulfinyl, halo-C C 6 alkylsulf
  • R 9 is halogen, nitro, cyano, CrC 6 alkyl, halo-C C 6 alkyl, C C 6 alkoxy, halo-C ⁇ -C 6 alkoxy, C 2 -C 6 alkenyl, halo-C 2 -C 6 alkenyI, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkoxy, C 3 - C 6 cycloalkylamino, C 3 -C 6 cycloaIkylthio, C 2 -C 6 alkenyloxy, halo-C 2 -C 6 alkenyloxy, C C 6 alkylthio, halo-C C 6 alkylthio, C C 6 alkylsulfonyloxy, halo-C r C 6 alkylsulfony!oxy, C C 6 alkylsulfinyl, halo-C ⁇ -C 6
  • W is O, S, S(O 2 ), N(R ! ) f C r C 6 alkyl or halo-d-C 6 alkyl;
  • Y is O, S or N(Rn);
  • Rn is C C 6 alkyl or unsubstituted or one- or poly-substituted phenyl; with the proviso that m and p are not equal to 0 at the same time; to their preparation and use in the control of endo- and ectoparasites, especially helminths, in and on warm-blooded productive livestock, domestic animals and plants, and also to pesticides which comprise at least one of these compounds.
  • amidoacetonitrile compounds with pesticidal action are disclosed in EP-0 953 565 A2, for example.
  • the active ingredients specifically revealed therein may not, however, always meet the requirements concerning strength and activity spectrum. There consequently exists a need for active ingredients with improved pesticidal properties. It has now been found that the amidoacetonitrile compounds of the formula I have outstanding pesticidal properties, in particular against endo- and ectoparasites in and on productive livestock, domestic animals and plants.
  • Alkyl - as group per se and as structural component of other groups and compounds, for example of haloalkyl, alkoxy, alkylthio, alkylsulfinyl and alkylsulfonyl, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, either straight-chain, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl.
  • Alkenyl - as group per se and as structural component of other groups and compounds - is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. alfyl, 2-butenyl, 3-pentenyl, 1-hexenyl or 1 ,3-hexadienyl, or branched, e.g. isopropenyl, isobutenyl, isoprenyl, tert-pentenyl or isohexenyl.
  • straight-chain e.g. alfyl, 2-butenyl, 3-pentenyl, 1-hexenyl or 1 ,3-hexadienyl, or branched, e.g. isopropenyl, isobutenyl, isoprenyl, tert-pentenyl or isohexenyl.
  • Alkynyl - as group per se and as structural component of other groups and compounds - is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. propargyl, 2-butynyl, 3-pentynyl, 1 -hexynyl, 1 -heptynyl or 3-hexen- 1-ynyl, or branched, e.g. 3-methylbut-1 -ynyl, 4-ethylpent-1 -ynyl or 4-methylhex-2-ynyl.
  • straight-chain e.g. propargyl, 2-butynyl, 3-pentynyl, 1 -hexynyl, 1 -heptynyl or 3-hexen- 1-ynyl, or branched, e.g. 3-methylbut-1 -ynyl, 4-ethylpent
  • Cycloalkyl - as group per se and as structural component of other groups and compounds, for example of halocycloalkyl, cycloalkoxy or cycloalkylthio, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • Aryl is phenyl or naphthyl, preferably phenyl.
  • Hetaryl is pyridyl, pyrimidyl, s-triazinyl, 1 ,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl or indazolyl, preferably pyridyl, pyrimidyl, s-triazinyl or 1 ,2,4-triazinyl, in particular pyridyl or pyrimidyl.
  • Halogen - as group per se and as structural component of other groups and compounds, such as of haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, - is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine, especially fluorine or chlorine.
  • Halogen-substituted carbon-comprising groups and compounds such as haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, can be partially halogenated or perhalogenated, it being possible, in the case of polyhalogenation, for the halogen substituents to be identical or different.
  • haloalkyl - as group per se and as structural component of other groups and compounds, such as of haloalkoxy or haloalkylthio, - are methyl substituted up to three times by fluorine, chlorine and/or bromine, such as CHF 2 or CF 3 ; ethyl substituted up to five times by fluorine, chlorine and/or bromine, such as CH 2 CF 3 , CF 2 CF 3 , CF 2 CCI 3) CF 2 CHCI 2 , CF 2 CHF 2 , CF 2 CFCI 2 , CF 2 CHBr 2 , CF 2 CHCIF, CF 2 CHBrF or CCIFCHCIF; propyl or isopropyl substituted up to seven times by fluorine, chlorine and/or bromine, such as CH 2 CHBrCH 2 Br, CF 2 CHFCF 3 , CH 2 CF 2 CF 3 or CH(CF 3 ) 2 ; butyl or one of its isomers substitute
  • Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms.
  • alkoxy is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, and also the pentyloxy and hexyloxy isomers; preferably methoxy and ethoxy.
  • Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms.
  • Haloalkoxy is, e.g., fluo ' romethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2-tetrafluoroethoxy, 2-fluoro- ethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
  • Ar is unsubstituted or one- or poly-substituted aryl; preferably one- or di-substituted aryl; (2) A compound of the formula I, wherein
  • R t is hydrogen, C C 6 alkyl, halo-C C 6 alkyl, allyl or CrC 6 alkoxymethyl; preferably hydrogen, C 1 -C 4 alkyl or halo-C C 4 alkyl; most preferably hydrogen or C ⁇ -C 2 alkyl;
  • R 2 , R 3 , R 4 , R 5 und R 6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted C 1 -C 4 alkyl, unsubstituted or one- or poly-substituted
  • R 2 and R 3 are together C 2 -C 4 alkylene; preferably either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted C C alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C r C 6 alkoxy and halo-C
  • R 2 and R 3 are together C 2 -C alkylene; most preferably, independently of one another, hydrogen or halogen;
  • R 7 and R 10 are, independently of each other, NH 2 , OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (d-C 6 -alkyl) 2 aminothiocarbonyl, phenylaminothiocarbonyl, C C 6 alkylsulfanylcarbonyl, C C 6 alkylcarbonylsulfanyl, halo-C 2 -
  • R 8 is halogen, nitro, cyano, d-C 6 alkyl, halo-d-C 6 alkyl, C ⁇ -C 6 alkoxy, halo-C r C 6 alkoxy, C 2 -C 6 alkenyl, halo-C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkoxy, C 3 - C 6 cycloalkylamino, C 3 -C 6 cycloalkylthio, C 2 -C 6 alkenyloxy, halo-C 2 -C 6 alkenyloxy, C C 6 alkylthio, halo-C C 6 alkenylthio, C 2 -C 6 alkenylthio, halo-C 2 -C 6 alkenylthio, d-Cealkylamino, di-
  • R 9 is halogen, nitro, cyano, C C 6 alkyl, halo-d-C 6 alkyl, C r C 6 alkoxy, halo ⁇ C C 6 alkoxy, C 2 -C 6 alkenyl, halo-C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkoxy, C 3 - C 6 cycloalky!amino, C 3 -C 6 cycloalkylthio, C 2 -C 6 alkenyloxy, halo-C 2 -C 6 alkenyloxy, C C 6 alkylthio, halo-d-C 6 alkylthio, Ci-Cealkylsulfinyl, halo-d-C 6 alkylsulfinyl, C r C 6 alkylsulfonyl, halo-C ⁇ -C
  • Ar is unsubstituted or one- or poly-substituted aryl
  • Ri is hydrogen, C r C 6 alkyl, halo-CrC 6 alkyl, allyl or C C 6 alkoxymethyl;
  • R 2 , 3 . R , 5 und Re are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted C C alkyl, unsubstituted or one- or poly-substituted
  • R 7 and R 10 are, independently of each other, NH 2 , OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (C 1 -C 6 -alkyl) 2 aminothiocarbony ) , phenylaminothiocarbonyl, C r C 6 alkylsulfanylcarbonyl, d-C 6 alkylcarbonylsulfanyl, halo-C 2 -
  • R 8 is halogen, nitro, cyano, C C 6 alkyl, halo-CrC 6 alkyl, d-C 6 alkoxy, halo-d-C 6 alkoxy,
  • R 9 is halogen, nitro, cyano, d-C 6 alkyl, halo-C C 6 alkyl, C r C 6 alkoxy, halo-d-C 6 alkoxy,
  • a is 1 , 2 or 3;
  • b is O, 1 , 2 or 3;
  • m, n, o and p are, independent of each other, 0, 1 , 2, 3 or 4;
  • W is O, S, S(O 2 ) or N(R 1 );
  • Y is O or S; with the proviso that m and p are not equal to 0 at the same time;
  • Ar is one- or di-substituted aryl
  • Hi is hydrogen, C C alkyl or halo-C r C 4 alkyl
  • R 2> 3 . 4> R5 und R 6 are either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted d-C alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen,
  • R 2 and R 3 are together C 2 -C 4 alkylene;
  • R 7 and R 10 are, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2- ha)o-(1 ,3)-dioxo)yl;
  • R 8 is halogen, cyano, C ⁇ -C 6 alkyl, halo-d-C 6 aIkyl, d-C 6 alkoxy, halo-Ci-Cealkoxy, unsubstituted or one- or poly-substituted phenyl, or unsubstituted or one- or poly-substituted phenoxy, whereby the substituents in each case can be independent of one another and are halogen; '
  • R 9 is halogen, cyano, C C 6 alkyl, halo-C C 6 alkyl, d-C e alkoxy, halo-C C 6 alkoxy, C 3 -
  • W is O or S
  • Y is O; with the proviso that m and p are not equal to 0 at the same time;
  • Ar is one- or di-substituted aryl
  • R t is hydrogen or C C 2 alkyl
  • R 2 ⁇ R 3 » R ⁇ 5 und R 6 are either, independently of one another, hydrogen or halogen;
  • R 7 and R 10 are, independently of each other, carboxy or aminocarbonyl
  • R 8 is halo-d-C ⁇ alkyl, or unsubstituted or one- or di-substituted phenoxy, whereby the substituents can be independent of one another and are halogen;
  • R 9 is halo-d-C 6 alkyl, halo-C C 6 alkoxy, haIo-C C 6 alkylthio, halo-C C 6 alkylsulfinyl or halo-
  • W and Y is O; with the proviso that m and p are not equal to 0 at the same time.
  • a further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is O, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula which is known or can be prepared by analogy to relevant known compounds and in which R ⁇ . R 2 . R3.
  • R 4 , R5, Re, R 7> Rs, W, a, b, m and n are as defined above in the formula I, with a compound of the formula
  • Ar, R 9 , R 10 , o and p are as defined above in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
  • the reactants can be reacted with one another as such, i.e. without addition of a solvent or diluent, e.g. in the molten form.
  • a solvent or diluent e.g. in the molten form.
  • solvents or diluents of: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachloroethene; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether,
  • Preferred leaving groups Q are OH, halogens, tosylates, mesylates and triflates, particularly preferably halogens, especially chlorine.
  • Suitable bases for facilitating the reaction are, e.g., alkali metal or alkaline earth metal hydroxides, hydrides, amides, alkoxides, acetates, carbonates, dialkylamides or alkyl- silylamides, alkylamines, alkylenediamines, if desired N-alkylated and saturated or unsaturated, cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines.
  • DBU ,5-diazabicyclo[5.4.0]undec-5-ene
  • the reaction is advantageously carried out at a temperature from approximately 0°C to approximately +150°C, preferably from approximately 20°C to approximately +100°C.
  • a further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is S, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula l, where Y is O, with a sulfonating agent, preferably P 4 S 10 , if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
  • a sulfonating agent preferably P 4 S 10
  • a further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is NRn, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula I, where Y is S, with a compound of formula NHRn, which is known or can be prepared by analogy to relevant known compounds and in which R-u is as defined above in the formula I, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
  • Salts of compounds I can be prepared in a way known per se.
  • acid addition salts of compound I are obtained by treatment with a suitable acid or a suitable ion- exchange reagent and salts with bases are obtained by treatment with a suitable base or a suitable ion-exchange reagent.
  • Salts of compounds I can be converted in the usual way to the free compounds I, acid addition salts, e.g. by treatment with a suitable basic agent or a suitable ion exchange reagent, and salts with bases, e.g. by treatment with a suitable acid or a suitable ion- exchange reagent.
  • Salts of compounds I can be changed in a way known per se to other salts of compounds I, acid addition salts for example to other acid addition salts, e.g. by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, e.g. with silver acetate, in a suitable solvent, in which an inorganic salt, e.g. silver chloride, being formed is insoluble and for this reason precipitates from the reaction mixture.
  • a salt of an inorganic acid such as a hydrochloride
  • a suitable metal salt such as a sodium, barium or silver salt
  • an acid e.g. with silver acetate
  • the compounds I with salt-forming properties can be obtained in the free form or in the form of salts.
  • the compounds I can also be obtained in the form of their hydrates and/or can incorporate other solvents, which might, for example, be used in the crystallization of compounds existing in the solid form.
  • the compounds I can exist in the form of one of the possible isomers or as a mixture of the same, e.g., according to the number, absolute and relative configuration of the asymmetric carbon atoms, as pure isomers, for example optical isomers and/or diastereoisomers, or as mixtures of isomers, such as mixtures of enantiomers, e.g. racemates, mixtures of diastereoisomers or racemate mixtures; the invention relates both to the pure isomers and to all possible mixtures of isomers and is to be correspondingly understood in each case heretofore and hereinafter, even if stereochemical details are not specifically referred to in every case.
  • Mixtures of diastereoisomers and mixtures of racemates of compounds l obtainable according to the process - depending on the choice of the starting materials and operating methods - or otherwise obtainable can be separated in a known way into the pure diastereoisomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
  • enantiomers such as racemates
  • optical isomers can be resolved into the optical isomers by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, e.g. high performance liquid chromatography (HPLC) on acetylcellulose, with the help of suitable microorganisms, by cleavage with specific immobilized enzymes, via the formation of inclusion complexes, e.g. by using chiral crown ethers, in which only one enantiomer is complexed.
  • HPLC high performance liquid chromatography
  • pure diastereoisomers or enantiomers according to the invention can also be obtained through generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the invention with educts with correspondingly suitable stereochemistry.
  • the biologically more effective isomer e.g. enantiomer, or mixture of isomers, e.g. mixture of enantiomers, is isolated or synthesized each time, provided that the individual components have different biological activity.
  • the invention in particular relates to the preparation process described in the example.
  • insects of the orders Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera.
  • ectoparasites which are a nuisance to man or animals and which transmit pathogens, for example flies, such as Musca domestica, Musca veiustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia im ' tans, and mosquitoes (Nematocera), such as Culicidae, Simuliidae, Psychodidae, but also bloodsucking parasites, for example fleas, such as Ctenocephalides felis and Ctenocephalides ca ⁇ is (cat and dog fleas), Xenopsylla cheopis, Pul
  • ticks are, e.g., Boophil ⁇ s, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros and the like, which preferably infest warm-blooded animals, including farm animals, such as cows, pigs, sheep and goats, poultry, such as chickens, turkeys and geese, fur-bearing animals, such as mink, foxes, chinchillas, rabbits and the like, and pets, such as cats and dogs, but also man.
  • farm animals such as cows, pigs, sheep and goats
  • poultry such as chickens, turkeys and geese
  • fur-bearing animals such as mink, foxes, chinchillas, rabbits and the like
  • pets such as cats and dogs, but also man.
  • the compounds I according to the invention are also effective against all or individual development stages of normally sensitive but also of resistant animal pests, such as insects and representatives of the order Acarina.
  • the insecticidal, ovicidal and/or acaricidal action of the active ingredients according to the invention may in the process be displayed directly, i.e. in killing the pests, which occurs immediately or only after some time, for example during moulting, or their eggs, or indirectly, e.g. in reduced egg laying and/or in a reduced hatching rate, in which the good action corresponds to a kill rate (mortality) of at least 50 to 60%.
  • the compounds I can also be used against hygiene pests, in particular of the order Diptera with the families Sarcophagidae, Anophilidae and Culicidae; of the orders Orthoptera, Dictyoptera (e.g. the family Blattidae) and Hymenoptera (e.g. the family Formicidae).
  • the compounds I also have lasting activity in the case of phytoparasitic mites and insects.
  • spider mites of the order Acarina they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.).
  • sucking insects of the order Homoptera are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera, Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders Lepidoptera, Coleoptera, Diptera and Orthoptera.
  • the compounds of the formula I are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others.
  • the compounds of the formula I are also active against plant nematodes of the genera Meloidogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus, Rizoglyphus and others.
  • the compounds are particularly active against helminths, among which the endoparasitic nematodes and trematodes can be the cause of serious diseases in mammals and poultry, e.g. in sheep, pigs, goats, cattle, horses, donkeys, dogs, cats, guinea pigs and ornamental birds.
  • Typical nematodes of this indication are: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Mention may specifically be made, among the trematodes, of the family of the Fasciolideae, in particular Fasciola hepatica. The particular advantage of the compounds of the formula I is their activity against such parasites, which are resistant to benzimidazole-based active ingredients.
  • Parasites of the families Filariidae and Setariidae are found in internal cell tissue and in organs, e.g. the heart, blood vessels, lymph vessels and subcutaneous tissue. Mention may particularly be made here of the dog heartworm, Dirofilaria immitis.
  • the compounds of the formula l are highly effective against these parasites.
  • the pests which can be controlled with the compounds of the formula I also include, from the class Cestoda (tapeworms), the families Mesocestoidae, in particular the genus Mesocestoides, especially M. lineatus; Dilepididae, in particular Dipylidium caninum, Joyeuxiella spp., especially Joyeuxiella pasquali, and Diplopylidium spp.; and Taeniidae, in particular Taenia pisiformis, Taenia cervi, Taenia ovis, Taenia hydatigena, Taenia multiceps, Taenia taeniaeformis, Taenia serialis and Echinocuccus spp., particularly preferably Taenia hydatigena, Taenia ovis, Taenia multiceps, Taenia serialis; Echinocuccus granulosus and Echinococcus granulosus and Echinococcus multilocularis, and Multiceps multiceps.
  • Taenia hydatigena T. pisiformis, T. ovis, T. taeniaeformis, Multiceps multiceps, Joyeuxiella pasquali, Dipylidium caninum, Mesocestoides spp., Echinococcus granulosus and E. multilocularis are controlled simultaneously with Dirofilaria immitis, Ancylostoma spp., Toxocara spp. and/or Trichuris vulpis on or in dogs and cats.
  • Ctenocephalides felis and/or C.canis are controlled simultaneously with the abovementioned nematodes and cestodes.
  • the compounds of the formula I are also suitable for controlling parasites which are pathogenic to man, among which may be mentioned, as typical representatives occurring in the digestive tract, those of the genera Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius.
  • the compounds of the present invention are also active against parasites of the genera Wuchereria, Brugia, Onchocerca and Loa from the family of the Filariidae, which occur in the blood, in tissue and in various organs, and also against Dracunculus and parasites of the genera Strongyloides and Trichinella, which specifically infect the gastrointestinal tract.
  • the compounds of the formula I are also active against harmful fungi which cause disease in plants and in man and animals.
  • the good pesticidal action of the compounds of the formula I according to the invention corresponds to a kill rate (mortality) of at least 50-60% of the pests mentioned.
  • the compounds of the formula I are characterized by an extraordinarily long duration of action.
  • the compounds of the formula I are used as such or preferably together with the auxiliaries conventional in formulation technology and can accordingly be processed in a known way, for example to emulsifiable concentrates, directly dilutable solutions, dilute emulsions, soluble powders, granules and also encapsulations in polymer substances.
  • the application methods as well as the compositions are chosen in accordance with the intended aims and the prevailing circumstances.
  • the formulation i.e. the compositions, preparations or combinations comprising the active ingredient of the formula I, or combinations of these active ingredients with other active ingredients, and, if desired, a solid or liquid additive, is prepared in a known way, for example by intimately mixing and/or grinding the active ingredients with extenders, for example with solvents, solid carriers and, if desired, surface-active compounds (surfactants).
  • extenders for example with solvents, solid carriers and, if desired, surface-active compounds (surfactants).
  • solvents such as ethanol, propanol or butanol, and glycols, and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, isophorone or diacetone alcohol, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide or water, vegetable oils, such as rapeseed oil, castor oil, coconut oil or soybean oil; and, if desired, silicone oils.
  • alcohols such as ethanol, propanol or butanol
  • glycols and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, isophorone
  • Preferred application forms for use in warm-blooded animals for controlling helminths include solutions, emulsions, suspensions (drenches), feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and pour-on formulations, care having to be taken over the physiological compatibility of the formulation auxiliaries.
  • Suitable binders for tablets and boluses are chemically modified polymeric natural products which are soluble in water or alcohol, such as starch, cellulose or protein derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxyethylcellulose, proteins, such as zein, gelatin, and the like), and synthetic polymers, for example polyvinyl alcohol, polyvinylpyrrolidone, and the like. Tablets also comprise fillers (e.g., starch, microcrystalline cellulose, sugar, lactose, and the like), lubricants and disintegrating agents.
  • fillers e.g., starch, microcrystalline cellulose, sugar, lactose, and the like
  • feed concentrates or compositions can, in addition to the active ingredients, also comprise additives, vitamins, antibiotics, chemotherapeutics, or other pesticides, mainly bacteriostats, fungistats, coccidiostats, or also hormone preparations, anabolics or substances which promote growth, influence the quality of meat from animals for slaughter or are useful to the organism in another way.
  • the finished feed or the finished drinking water comprises the active ingredients preferably in a concentration from approximately 0.0005 to 0.02% by weight (5-200 ppm).
  • the compounds of the formula I according to the invention can be used alone or in combination with other biocides. They can, e.g., be combined with pesticides possessing the same direction of action, in order to enhance the action, or can be combined with substances possessing another direction of action, in order to broaden the activity spectrum. It may also make sense to add substances which repel, known as repellents.
  • the compounds of the formula I are appropriately combined with substances having endoparasiticidal properties. They can also, naturally, be used in combination with antibacterial compositions. Since the compounds of the formula I represent adulticides, i.e. since they are effective in particular against the adult stages of the target parasites, the addition of pesticides which are more likely to attack the juvenile stages of parasites can be highly advantageous. In this way, most of those parasites causing great economic damage are namely included. In addition, a substantial contribution is also made as well to avoiding the formation of resistance. Some combinations can also lead to synergistic effects, i.e. that the total amount of active substance consumed can be reduced, which is desirable from an ecological viewpoint. Preferred groups of combination participants and particularly preferred combination participants are mentioned subsequently, which combinations can, in addition to a compound of the formula I, comprise one or more of these participants.
  • Suitable participants in the mixture include biocides, for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellents or detachers.
  • biocides for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellent
  • Nonlimiting examples of suitable insecticides and acaricides are: 1. Abamectin 8. Aiphamethrin 15. Bacillus subtil, toxin 2. AC 303 630 9. Amitraz 16. Bendiocarb 3. Acephate 10. Avermectin B ⁇ 17. Benfuracarb 4. Acrinathrin 11. AZ 60541 18. Bensultap 5. Alanycarb 12. Azinphos E 19. ⁇ -Cyfluthrin 6. Aldicarb 13. Azinphos-methyl 20. Bifenthrin 7. ⁇ -Cypermethrin 14. Azocyclotin 21. BPMC 22. Brofenprox 55. Dimethoate 88. Formothion
  • Clocythrin 73 Fenothiocarb 105. ⁇ -Cyhalothrin
  • Nonlimiting examples of suitable anthelmintics are mentioned subsequently, in which some representatives, in addition to the anthelmintic activity, also have an insecticidal and acaricidal activity and are already included in the above list:
  • Omphalotin a macrocyclic fermentation product from the fungus Omphalotus olearius disclosed in WO 97/20857
  • Abamectin Avermectin B1
  • Ivermectin 22,23-Dihydroavermectin B1
  • Moxidectin 5-O-Demethyl-28-deoxy-25-(1 ,3-dimethyl-1-butenyl)-6,28-epoxy-23- (methoxyimino)milbe ycin B
  • Doramectin 25-Cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)avermectin A1a
  • Milbemectin Mixture of Milbemycin A3 and Milbemycin A4 (A12)
  • Milbemycin oxime 5-Oxime of Milbemectin
  • Nonlimiting examples of suitable repelling substances are:
  • LV A preparation comprising insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 1266; Beauve ⁇ a brogniartii, from The Pesticide Manual, 11 ,h Ed. (1997), The British Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide Manual, 11 th Ed. (1997), The British Crop Protection Council, London, page 83;
  • LPI A preparation comprising insect-active viruses, preferably Neodipridon Sertifer NPV, from The Pesticide Manual, 11 lh Ed. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11 h Ed. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus, from The Pesticide Manual, 11 th Ed.
  • insect-active viruses preferably Neodipridon Sertifer NPV
  • Neodipridon Sertifer NPV from The Pesticide Manual, 11 lh Ed.
  • Mamestra brassicae NPV from The Pesticide Manual, 11 h Ed.
  • Cydia pomonella granulosis virus from The Pesticide Manual, 11 th Ed.
  • a further essential aspect of the present invention relates to combination preparations for the control of parasites on warm-blooded animals, characterised in that they contain, in addition to a compound of formula I, at least one further active ingredient having the same or different sphere of activity and at least one physiologically acceptable carrier.
  • the present invention is not restricted to two-fold combinations.
  • Especially preferred combination partners for the compounds of the formula I of the present inventions are the more modern natural or chemically modified macrocyclic lactones (macrolides), such as avermectins, milbemycins and derivatives thereof, including prominent representatives such as Ivermectin, Doramectin, Moxidectin, Selamectin, Emamectin, Eprinomectin, Milbemectin, Abamectin, Milbemycin oxime, Nemadectin, and a derivative thereof, in the free form or in the form of a physiologically acceptable salt.
  • macrocyclic lactones such as avermectins, milbemycins and derivatives thereof, including prominent representatives such as Ivermectin, Doramectin, Moxidectin, Selamectin, Emamectin, Eprinomectin, Milbemectin, Abamectin, Milbemycin oxime, Nemadectin
  • a further advantage of the combination product is the pest resistance management, meaning that the occurrence of resistance against the compounds of the formula I can drastically be delayed by the administration of the combination product instead of applying the compounds of formula I only. Another advantage is that the combination product can successfully be used even in those cases where the worm population has already developed resistance against a macrocyclic lactones.
  • a major advantage of the compounds of the formula 1 is their exhibiting full efficacy against worms resistant to commonly used products such as representatives of the macrocyclic lactones, e.g. Ivermectin or Moxidectin, and to Levamisole or representatives of the benzimidazole class of anthelmintics.
  • the macrocyclic lactones are most preferred because they exhibit a broad spectrum of activity. Most of them exhibit ecto- and in parallel endo-parsiticidal activity. Therefore, they are also called endectocides. Macrocyclic lactones bind to gluta ated chlorine channels causing paralysis of the parasites in the first instance, followed by their death.
  • R 4 is hydroxyl, -NH-CH 3 or -NH-OCH 3 ;
  • Ivermectin is 22,23-Dihydroabamectin; 22,23-dihydroavermectin B1 ; or 22,23-dihydro-C- 076B1 , wherein X is -C(H)(OH)- ; Y is -C(H 2 )-; R 1 is the radical
  • R 2 is either -CH(CH 3 )-CH 3 or -CH(CH 3 )-C 2 H 5 and the bond between atoms 22 and 23 represents a single bond.
  • Ivermectin is known from US-4,199,569.
  • R 2 is cyclohexyl and the bond between atoms 22 and 23 represents a double bond.
  • Doramectin is known from US-5,089,480.
  • R 2 is cyclohexyl; and the bond between atoms 22 and 23 represents a single bond.
  • Selamectin is known e.g. from: ECTOPARASITE ACTIVITY OF SELAMECTIN; A novel endectocide for dogs and cats. A Pfizer Symposium, held in conjunction with The 17th international Conference of the World Association for the Advancement of Veterinary Parasitology, 19 August 1999. Copenhagen, Denmark.
  • R 2 is -CH(CH 3 )-CH 3 , or -CH(CH 3 )-C 2 H 5 , and the bond between atoms 22 and 23 represents a double bond.
  • Emamectin is known from US-4,874,749.
  • R 2 is -CH(CH 3 )-CH 3 , or -CH(CH 3 )-C 2 H 5 , and the bond between atoms 22 and 23 represents a double bond.
  • Eprinomectin is known from US-4,427,663.
  • Milbemectin is (6R,25R)-5-0-demethyl-28-deoxy-6,28-epoxy-25-methylmilbemycin, wherein X is -C(H)(OH)- ; Y is -C(H 2 )-; is hydrogen; R 2 is -CH 3 , or -C 2 H 5 ; and the bond between atoms 22 and 23 represents a single bond. Milbemectin is known from US- 3,950,360.
  • R 2 is -CH(CH 3 )-CH 3 , or -CH(CH 3 )-C 2 H 5 ; and the bond between atoms 22 and 23 represents a double bond.
  • Abamectin is known from US-4,310,519.
  • Milbemycin oxi is milbemycin A4 5-oxime; milbemycin A3 5-oxime, wherein X is - C(H)(OH)- ; Y is -C(H 2 )-; R is hydrogen; R 2 is -CH(CH 3 )-CH 3 , or -CH(CH 3 )-C 2 H 5 , and the bond between atoms 22 and 23 represents a single bond. Milbemycin oxim is known from US-4,547,520.
  • R 2 is -CH 3 or C 2 H 5 , and the bond between atoms 22 and 23 represents a single bond. This compound is known from WO 01/83500.
  • Nemadectin is known from US-4,869,901.
  • Especially preferred combination partners are Ivermectin, Abamectin and Moxidectin.
  • the anthelmintic compositions according to the invention generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of active ingredient of the formula I or mixtures thereof, and 99.9 to 1% by weight, in particular 99.8 to 5% by weight, of a solid or liquid additive, including 0 to 25% by weight, in particular 0.1 to 25% by weight, of a surfactant.
  • compositions according to the invention can be applied topically, perorally, parenterally or subcutaneously to the animals to be treated, the compositions being present in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses, capsules and as pour-on formulations.
  • the pour-on or spot-on method consists in applying the compound of the formula I to a locally restricted part of the skin or fur, advantageously on the neck or back of the animal. This is carried out, e.g., by applying a spot or dash of the pour-on or spot-on formulation to a relatively small area of the fur, from where the active substance spreads out virtually unaided over wide regions of the fur because of the spreading components of the formulation and supported by the movements of the animal.
  • lt is advantageous for pour-on or spot-on formulations to comprise carriers which promote speedy distribution on the surface of the skin or in the fur of the host animal and which are generally described as spreading oils.
  • Suitable carriers are, e.g., oily solutions; alcoholic and isopropanolic solutions, for example solutions of 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxal ester, oleyl oleate, decyl oleate, hexyl laurate, capric acid esters of saturated fatty alcohols with a chain length of C ⁇ 2 -C ⁇ 8 ; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate or di(n-butyl) adipate, or also solutions of esters of aliphatic acids, e.g.
  • glycols It can be advantageous if a dispersant known from the pharmaceutical or cosmetics industry is additionally present.
  • examples are 2-pyrrolidone, 2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and ethers and esters thereof, propylene glycol or synthetic triglycerides.
  • the oily solutions include, e.g., vegetable oils, such as olive oil, groundnut oil, sesame oil, pine oil, linseed oil or castor oil.
  • vegetable oils can also be present in epoxidized form. Paraffin oils and silicone oils can also be used.
  • a pour-on or spot-on formulation comprises 1 to 20% by weight of a compound of the formula I, 0.1 to 50% by weight of dispersant and 45 to 98.9% by weight of solvent.
  • the pour-on or spot-on method can be used particularly advantageously with gregarious animals, such as cattle, horses, sheep or pigs, where it is difficult or time-consuming to treat all the animals orally or via injection. Because of its simplicity, this method can naturally also be used with all other animals, including individual domestic animals or pets, and is very popular with animal owners because it can often be implemented without the expert assistance of a veterinary surgeon.
  • compositions can comprise yet further additives, such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects.
  • additives such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects.
  • Such anthelmintic compositions used by the end user likewise form part of the present invention.
  • the active ingredients of the formula I can be used in all their steric configurations or mixtures thereof.
  • the invention also includes a method for the prophylactic protection of warm-blooded animals, in particular of productive livestock, domestic animals and pets, against parasitic helminths, which comprises applying the active ingredients of the formula I or the active ingredient formulations prepared therefrom as a feed additive or drinking water additive or also in the solid or liquid form, orally, by injection or parenterally, to the animals.
  • the invention also includes the compounds of the formula 1 according to the invention for use in one of the methods mentioned.
  • Preferred formulations are in particular composed in the following way:
  • the active ingredient is dissolved in methylene chloride and sprayed onto the carrier, and the solvent is subsequently evaporated under reduced pressure. Such granules can be added to the animal feed.
  • the finely milled active ingredient is applied evenly in a mixer to the kaolin, which has been moistened with polyethylene glycol. In this way, dust-free coated granules are obtained.
  • Oilv vehicle slow release
  • Active ingredient 0.1-1.0 g Groundnut oil ad 100 ml
  • Active ingredient 0.1-1.0 g Sesame oil ad 100 ml
  • Aqueous solubilisate (rapid release) 1. Active ingredient 0.1-1.0 g Polyethoxylated castor oil (40 ethylene oxide units) 10 g 1 ,2-Propanediol 20 g Benzyl alcohol 1 g Water for injections ad 100 ml 2.
  • Active ingredient 0.1-1.0 g Polyethoxylated sorbitan monooleate (20 ethylene oxide units) 8 g 4-Hydroxymethyl-1 ,3-dioxolane (glycerol formal) 20 g Benzyl alcohol 1 g Water for injections ad 100 ml
  • Preparation The active ingredient is dissolved in the solvents and the surfactant and made up to the required volume with water. Sterile filtration is carried out through a suitable membrane filter with a pore diameter of 0.22 ⁇ m.
  • the aqueous systems can preferably also be used for oral and/or intraruminal administration.
  • compositions can also comprise further additives, such as stabilizers, e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil), antifoaming agents, e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects.
  • stabilizers e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil)
  • antifoaming agents e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects.

Abstract

The invention relates to compounds of the general formula (I) wherein Ar, R1, R2, R3, R4, R5, R6, R7, R8, R9, R1o, W, a, b, m, n, o and p are as defined in claim 1, and to any enantiomers thereof. The active ingredients have advantageous pesticidal properties. They are particularly suitable for controlling parasites in warm-blooded animals.

Description

AMINOACETONITRILE DERIVATIVES AND THEIR USE FOR CONTROLLING PARASITES ON WARM-BLOODED ANIMALS
The present invention relates to new amidoacetonitπ'le compounds of the formula
Figure imgf000002_0001
wherein
Ar is unsubstituted or one- or poly-substituted aryl or hetaryl;
R is hydrogen, C C6alkyl, halo-CrC6alkyl, CrC6-alkylcarbonyl, Cι-C6alkoxycarbonyl, allyl, C C6alkoxymethyl, unsubstituted or one- or poly-substituted phenylcarbonyl, Cr C6alkylsulfonyl or unsubstituted or one- or poly-substituted phenylsulfonyl;
R2, R3, R4, R5 und R6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted CrC6alkyl, unsubstituted or one- or poly-substituted C2-C6alkenyl, unsubstituted or one- or poly-substituted C2-C6alkinyl, unsubstituted or one- or poly-substituted CrC6alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C^Cealkoxy and halo-Cr C6alkoxy; unsubstituted or one- or poly-substituted C3-C6cycloalkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen and C C6alkyl; or unsubstituted or one- or poly-substituted phenyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, CrC6alkyl, halo-C C6a!kyl, CrC6alkoxy, halo-C C6alkoxy, CrC6alkylthio, halo-CrC6alkylthio, CrC6alkylsuIfinyl, halo-CrC6alkylsulfinyl, C C6alkylsulfonyl, halo-Cι-C6alkylsulfonyl, CrCβalkylamino and di-C Cβalkylamino; or R2 and R3 are together C2-C6alkylene;
R7 and R10 are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, unsubstituted or one- or poly- substituted phenylthiocarbamido, unsubstituted or one- or poly-substituted Cr C6alkylthiocarbamido, unsubstituted or one- or poly-substituted Ct-Cβalkoxythiocarbamido, unsubstituted or one- or poly-substituted phenyloxythiocarbamido, unsubstituted or one- or poly-substituted phenylaminothiocarboxy, unsubstituted or one- or poly-substituted phenyloxythiocarboxy, unsubstituted or one- or poly-substituted phenylaminothiocarboxamido, unsubstituted or one- or poly-substituted C C6alkylaminothiocarbonyl, (CrC6-alkyl)2aminothiocarbonyl, phenylaminothiocarbonyl, unsubstituted or one- or poly-substituted phenylsulfanylcarbonyl, unsubstituted or one- or poly-substituted benzylsulfanylcarbonyl, unsubstituted or one- or poly-substituted phenylsulfanyl-C C6alkyl, unsubstituted or one- or poly-substituted phenyl-Cr C6alkylsulfanyl, C C6aIkylsulfanylcarbonyl, CrC6alkylcarbonylsulfanyl, unsubstituted or one- or poly-substituted phenylcarbonylsulfanyl, halo-C2-C6alkynyl, C C6alkylaminothiocarboxy, C C6alkyloxythiocarboxy, CrC6alkylaminothiocarboxamido, (1 ,3)-oxathiolyl, 2-halo-(1 ,3)- oxathiolyl, (1 ,3)-dioxolyl, 2-halo-(1 ,3)-dioxolyl, sulfonyl, aminosulfonyl, C C6alkylaminosulfonyl, di-CrC6alkylaminosulfonyl, unsubstituted or one- or poly-substituted arylaminosulfonyl, unsubstituted or one- or poly-substituted arylsulfonyloxy, unsubstituted or one- or poly-substituted arylsulfonylamino, unsubstituted or one- or poly-substituted aryloxysulfonyl, CrC6alkyloxysulfonyl, CrC6alkylaminocarbonylsulfanyl, unsubstituted or one- or poly-substituted phenylaminocarbonylsulfanyl, unsubstituted or one- or poly- substituted phenoxythiocarbonyl, unsubstituted or one- or poly-substituted phenylsulfanylthiocarbonyl, or CrC6alkyloxythiocarbonyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of Ri and halogen;
R8 is halogen, nitro, cyano, C C6alkyl, halo-C C6alkyl, d-Cealkoxy, halo-C C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C -C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-CrC6alkylthio, C C6alkylsulfonyloxy, halo-C C6alkylsulfonyloxy, C C6alkylsulfinyl, halo-C C6alkylsulfinyl, C C6alkylsulfonyl, halo-CrC6alkylsulfonyl, C2- C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2- C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C C6alkylamino, di-C C6alkylamino, C C6alkylsulfonylamino, halo-CrC6alkylsulfonylamino, C C6alkylcarbonyl, halo-C C6alkylcarbonyl, CrC6alkoxycarbonyl, d-Cβalkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly- substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenylmethoximino, unsubstituted or one- or poly-substituted phenylhydroxymethyl, unsubstituted or one- or poly- substituted 1-phenyl-1-hydroxy ethyl, unsubstituted or one- or poly-substituted phenylchloromethyl, unsubstituted or one- or poly-substituted phenylcyanomethyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, unsubstituted or one- or poly-substituted phenylacetylenyl, unsubstituted or one- or poly-substituted pyridyloxy, or unsubstituted or one- or poly-substituted phenylsulfanyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of RT and halogen;
R9 is halogen, nitro, cyano, CrC6alkyl, halo-C C6alkyl, C C6alkoxy, halo-Cι-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyI, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloaIkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-C C6alkylthio, C C6alkylsulfonyloxy, halo-CrC6alkylsulfony!oxy, C C6alkylsulfinyl, halo-Cι-C6aIkylsulfinyl, C C6alkylsulfonyl, halo-CrC6alkylsulfonyl, C2- C6a)kenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2- C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, d-C-ealkylamino, di-CrC6alkylamino, d- C6alkylsulfony!amino, halo-CrC6alkylsulfonylamino, d-C6alkylcarbonyl, halo-Cr C6alkylcarbonyl, d-C6alkoxycarbonyl, CrC6alkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly- substituted arylsulfonyl, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenylmethoximino, unsubstituted or one- or poly- substituted phenylhydroxymethyl, unsubstituted or one- or poly-substituted 1-p-phenyl-1- hydroxyethyl, unsubstituted or one- or poly-substituted phenylchlormethyl, unsubstituted or one- or poly-substituted phenylcyanomethyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, unsubstituted or one- or poly- substituted phenylacetylenyl, unsubstituted or one- or poly-substituted phenoxy, or pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of R^ and halogen; a is 1 , 2, 3 or 4; b is 0, 1 , 2, 3 or 4; m, n, o and p are, independent of each other, 0, 1 , 2, 3, 4 or 5;
W is O, S, S(O2), N(R!)f CrC6alkyl or halo-d-C6alkyl;
Y is O, S or N(Rn); and
Rn is C C6alkyl or unsubstituted or one- or poly-substituted phenyl; with the proviso that m and p are not equal to 0 at the same time; to their preparation and use in the control of endo- and ectoparasites, especially helminths, in and on warm-blooded productive livestock, domestic animals and plants, and also to pesticides which comprise at least one of these compounds.
Substituted amidoacetonitrile compounds with pesticidal action are disclosed in EP-0 953 565 A2, for example. The active ingredients specifically revealed therein may not, however, always meet the requirements concerning strength and activity spectrum. There consequently exists a need for active ingredients with improved pesticidal properties. It has now been found that the amidoacetonitrile compounds of the formula I have outstanding pesticidal properties, in particular against endo- and ectoparasites in and on productive livestock, domestic animals and plants.
Alkyl - as group per se and as structural component of other groups and compounds, for example of haloalkyl, alkoxy, alkylthio, alkylsulfinyl and alkylsulfonyl, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, either straight-chain, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl.
Alkenyl - as group per se and as structural component of other groups and compounds - is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. alfyl, 2-butenyl, 3-pentenyl, 1-hexenyl or 1 ,3-hexadienyl, or branched, e.g. isopropenyl, isobutenyl, isoprenyl, tert-pentenyl or isohexenyl.
Alkynyl - as group per se and as structural component of other groups and compounds - is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. propargyl, 2-butynyl, 3-pentynyl, 1 -hexynyl, 1 -heptynyl or 3-hexen- 1-ynyl, or branched, e.g. 3-methylbut-1 -ynyl, 4-ethylpent-1 -ynyl or 4-methylhex-2-ynyl.
Cycloalkyl - as group per se and as structural component of other groups and compounds, for example of halocycloalkyl, cycloalkoxy or cycloalkylthio, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
Aryl is phenyl or naphthyl, preferably phenyl.
Hetaryl is pyridyl, pyrimidyl, s-triazinyl, 1 ,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl or indazolyl, preferably pyridyl, pyrimidyl, s-triazinyl or 1 ,2,4-triazinyl, in particular pyridyl or pyrimidyl.
Halogen - as group per se and as structural component of other groups and compounds, such as of haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, - is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine, especially fluorine or chlorine.
Halogen-substituted carbon-comprising groups and compounds, such as haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, can be partially halogenated or perhalogenated, it being possible, in the case of polyhalogenation, for the halogen substituents to be identical or different. Examples of haloalkyl - as group per se and as structural component of other groups and compounds, such as of haloalkoxy or haloalkylthio, - are methyl substituted up to three times by fluorine, chlorine and/or bromine, such as CHF2 or CF3; ethyl substituted up to five times by fluorine, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CCI3) CF2CHCI2, CF2CHF2, CF2CFCI2, CF2CHBr2, CF2CHCIF, CF2CHBrF or CCIFCHCIF; propyl or isopropyl substituted up to seven times by fluorine, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CH2CF2CF3 or CH(CF3)2; butyl or one of its isomers substituted up to nine times by fluorine, chlorine and/or bromine, such as CF(CF3)CHFCF3 or CH2(CF2)2CF3; pentyl or one of its isomers substituted up to eleven times by fluorine, chlorine and/or bromine, such as CF(CF3)(CHF)2CF3 or CH2(CF2)3CF3; and hexyl or one of its isomers substituted up to thirteen times by fluorine, chlorine and/or bromine, such as (CH2)4CHBrCH2Br, CF2(CHF)4CF3, CH2(CF2)4CF3 or C(CF3)2(CHF)2CF3.
Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms. For example, alkoxy is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, and also the pentyloxy and hexyloxy isomers; preferably methoxy and ethoxy. Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms. Haloalkoxy is, e.g., fluo'romethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1 ,1 ,2,2-tetrafluoroethoxy, 2-fluoro- ethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.
Preferred embodiments within the context of the invention are:
(1) A compound of the formula I, wherein
Ar is unsubstituted or one- or poly-substituted aryl; preferably one- or di-substituted aryl; (2) A compound of the formula I, wherein
Rt is hydrogen, C C6alkyl, halo-C C6alkyl, allyl or CrC6alkoxymethyl; preferably hydrogen, C1-C4alkyl or halo-C C4alkyl; most preferably hydrogen or Cι-C2alkyl;
(3) A compound of the formula I, wherein
R2, R3, R4, R5 und R6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted C1-C4alkyl, unsubstituted or one- or poly-substituted
C2-C4alkenyl, unsubstituted or one- or poly-substituted C2-C4alkinyl or unsubstituted or one- or poly-substituted C C4alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, d-C6alkoxy and halo-
C C6alkoxy; or R2 and R3 are together C2-C4alkylene; preferably either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted C C alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, CrC6alkoxy and halo-C
C6alkoxy; or R2 and R3 are together C2-C alkylene; most preferably, independently of one another, hydrogen or halogen;
(4) A compound of the formula I, wherein
R7 and R10 are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (d-C6-alkyl)2aminothiocarbonyl, phenylaminothiocarbonyl, C C6alkylsulfanylcarbonyl, C C6alkylcarbonylsulfanyl, halo-C2-
C6alkynyl, d-C6alkylaminothiocarboxy, C C6alkyloxythiocarboxy, C
C6alkylaminothiocarboxamido, (1,3)-oxathiolyl, 2-halo-(1,3)-oxathiolyl, (1,3)-dioxolyl, 2-halo-
(1 ,3)-dioxolyl, sulfonyl, aminosulfonyl, CrC6alkylaminosulfonyl, di-Cι-C6alkylaminosulfonyl, d-C6alkyloxysulfonyl, d-C6alkylaminocarbonylsulfanyl, or Cι-C6alkyloxythiocarbonyl; preferably, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2-halo-
(1 ,3)-dioxolyl; preferably, independently of each other, carboxy, aminocarbonyl, (1,3)-dioxolyl or 2-halo-
(1 ,3)-dioxolyl; most preferably, independently of each other, carboxy or aminocarbonyl;
(5) A compound of the formula I, wherein
R8 is halogen, nitro, cyano, d-C6alkyl, halo-d-C6alkyl, Cι-C6alkoxy, halo-CrC6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-C C6alkylthio, C2-C6alkenylthio, halo-C2-C6alkenylthio, d-Cealkylamino, di-
Cι-C6alkylamino, C C-6alkylcarbonyl, halo-d-C6alkylcarbonyI, C C6alkoxycarbonyl, Cr
C6alkylaminocarbonyl, di-Cι-C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, or unsubstituted or one- or poly-substituted pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of R^ and halogen; preferably halogen, cyano, d-C6alkyl, halo-d-C6alkyl, d-C6alkoxy, halo-d-C6alkoxy, unsubstituted or one- or poly-substituted phenyl, or unsubstituted or one- or poly-substituted phenoxy, whereby the substituents in each case can be independent of one another and are halogen; most preferably halo-d-C6alkyl, or unsubstituted or one- or di-substituted phenoxy, whereby the substituents can be independent of one another and are halogen;
(6) A compound of the formula I, wherein
R9 is halogen, nitro, cyano, C C6alkyl, halo-d-C6alkyl, CrC6alkoxy, halo~C C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalky!amino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-d-C6alkylthio, Ci-Cealkylsulfinyl, halo-d-C6alkylsulfinyl, CrC6alkylsulfonyl, halo-Cι-C6alky1sulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo- C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, d-C6alkylcarbonyl, halo-d-C6alkylcarbonyl or CrC6alkoxycarbonyl; preferably halogen, cyano, d-C6alkyl, halo-d-C6alkyl, Cι-C6alkoxy, halo-d-Cealkoxy, C3- C6cycloalkylthio, d-C6alkylthio, halo-CrC6alkylthio, Cι-C6alkylsulfinyl, halo-C C6alkylsulfinyl, C C6alkylsulfonyl or halo-CrC6alkylsulfonyl; most preferably halo-d-C6alkyl, halo-d-C6alkoxy, halo-d-C6alkylthio, halo-d~C6alkylsulfinyl or halo-d-C6a!kylsulfonyl;
(7) A compound of the formula I, wherein a is 1 , 2 or 3; preferably 1 or 2; most preferably 1 ;
(8) A compound of the formula I, wherein b is 0, 1 , 2 or 3; preferably 0, 1 or 2; most preferably 0;
(9) A compound of the formula I, wherein m, n, o and p are, independent of each other, 0, 1 , 2, 3 or 4; preferably, independent of each other, 0, 1 , 2 or 3; more preferably, independent of each other, 0, 1 or 2; most preferably, independent of each other, 0 or 1 ; with the proviso that m and p are not equal to 0 at the same time;
(10) A compound of the formula I, wherein W is O, S, S(02) or N(R1); preferably O or S; most preferably O;
(11) A compound of the formula I, wherein Y is O or S; preferably O;
(12) A compound of the formula I, wherein
Ar is unsubstituted or one- or poly-substituted aryl;
Ri is hydrogen, CrC6alkyl, halo-CrC6alkyl, allyl or C C6alkoxymethyl;
R2, 3. R , 5 und Re are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted C C alkyl, unsubstituted or one- or poly-substituted
C2-C4alkenyl, unsubstituted or one- or poly-substituted C2-C4alkinyl or unsubstituted or one- or poly-substituted d-C4alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, d-C6alkoxy and halo- d-C6a!koxy; or R2 and R3 are together C2-C4alkylene;
R7 and R10 are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (C1-C6-alkyl)2aminothiocarbony), phenylaminothiocarbonyl, CrC6alkylsulfanylcarbonyl, d-C6alkylcarbonylsulfanyl, halo-C2-
C6alkynyl, CrC-6alkylaminothiocarboxy, C C6alkyloxythiocarboxy, d-
C6alkylaminothiocarboxamido, (1 ,3)-oxathiolyl, 2-halo-(1 ,3)-oxathiolyl, (1 ,3)-dioxolyl, 2-halo-
(1 ,3)-dioxolyl, sulfonyl, aminosulfonyl, CrC6alkylaminosulfonyl, di-CrC6alkylaminosulfonyl,
C C6alkyloxysulfonyl, CrC6alkylaminocarbonylsulfanyl, or C C6alkyloxythiocarbonyl;
R8 is halogen, nitro, cyano, C C6alkyl, halo-CrC6alkyl, d-C6alkoxy, halo-d-C6alkoxy,
C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C
C6alkylthio, halo-CrC6alkylthio, C2-C6alkenylthio, halo-C2-C6alkeny!thio, d-C6alkylamino, di- d-C6alkylamino, CrC6alkylcarbonyl, halo-d-C6alkylcarbonyl, d-C6alkoxycarbonyl, C
C6alkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, or unsubstituted or one- or poly-substituted pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of R^ and halogen;
R9 is halogen, nitro, cyano, d-C6alkyl, halo-C C6alkyl, CrC6alkoxy, halo-d-C6alkoxy,
C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3-
C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, d-
C6alkylthio, halo-C C6alkylthio, d-Cealkylsulfinyl, halo-CrC6alkylsulfinyl, C C6alkylsulfonyl, halo-Cι-C6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-
C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, CrC6alkylcarbonyl, halo-C C6alkylcarbonyl or C C6alkoxycarbonyl; a is 1 , 2 or 3; b is O, 1 , 2 or 3; m, n, o and p are, independent of each other, 0, 1 , 2, 3 or 4;
W is O, S, S(O2) or N(R1); and
Y is O or S; with the proviso that m and p are not equal to 0 at the same time;
(13) A compound of the formula I, wherein
Ar is one- or di-substituted aryl;
Hi is hydrogen, C C alkyl or halo-CrC4alkyl;
R2> 3. 4> R5 und R6 are either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted d-C alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen,
Cι-C6alkoxy and halo-CrC6alkoxy; or R2 and R3 are together C2-C4alkylene;
R7 and R10 are, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2- ha)o-(1 ,3)-dioxo)yl;
R8 is halogen, cyano, Cι-C6alkyl, halo-d-C6aIkyl, d-C6alkoxy, halo-Ci-Cealkoxy, unsubstituted or one- or poly-substituted phenyl, or unsubstituted or one- or poly-substituted phenoxy, whereby the substituents in each case can be independent of one another and are halogen; '
R9 is halogen, cyano, C C6alkyl, halo-C C6alkyl, d-Cealkoxy, halo-C C6alkoxy, C3-
C6cycloalkylthio, Cι-C6alkylthio, halo-C C6alkylthio, C C6alkylsulfinyl, halo-C C6alkylsυlfinyl,
C C6alkylsulfonyl or halo-d-C6alkylsulfonyl; a is 1 or 2; b is 0, 1 or 2; m, n, o and p are, independent of each other, 0, 1, 2 or 3;
W is O or S; and
Y is O; with the proviso that m and p are not equal to 0 at the same time;
(14) A compound of the formula I, wherein
Ar is one- or di-substituted aryl;
Rt is hydrogen or C C2alkyl;
R2ι R3» R τ 5 und R6 are either, independently of one another, hydrogen or halogen;
R7 and R10 are, independently of each other, carboxy or aminocarbonyl;
R8 is halo-d-Cβalkyl, or unsubstituted or one- or di-substituted phenoxy, whereby the substituents can be independent of one another and are halogen;
R9 is halo-d-C6alkyl, halo-C C6alkoxy, haIo-C C6alkylthio, halo-C C6alkylsulfinyl or halo-
CrC6alkylsulfonyl; a is 1 ; b is O; m, n, o and p are, independent of each other, 0 or 1 ;
W and Y is O; with the proviso that m and p are not equal to 0 at the same time.
The compounds of the formula I listed in Table 1 are particularly preferred within the context of the invention and the compounds of the formula I mentioned in the synthetic examples are very particularly preferred.
A further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is O, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula
Figure imgf000012_0001
which is known or can be prepared by analogy to relevant known compounds and in which Rι. R2. R3. R4, R5, Re, R7> Rs, W, a, b, m and n are as defined above in the formula I, with a compound of the formula
Figure imgf000012_0002
which is known or can be prepared by analogy to relevant known compounds and in which
Ar, R9, R10, o and p are as defined above in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
That which has been said above for salts of compounds I applies analogously to starting materials mentioned hereinabove and hereinafter with regard to the salts thereof.
The reactants can be reacted with one another as such, i.e. without addition of a solvent or diluent, e.g. in the molten form. For the most part, however, it is advantageous to add an inert solvent or diluent or a mixture thereof. Mention may be made, as examples of such solvents or diluents, of: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachloroethene; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydrofuran or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; amides, such as N,N-dimethyl- formamide, N,N-diethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoramide; nitriles, such as acetonitrile or propionitrile; and sulfoxides, such as dimethyl sulfoxide.
Preferred leaving groups Q are OH, halogens, tosylates, mesylates and triflates, particularly preferably halogens, especially chlorine.
Suitable bases for facilitating the reaction are, e.g., alkali metal or alkaline earth metal hydroxides, hydrides, amides, alkoxides, acetates, carbonates, dialkylamides or alkyl- silylamides, alkylamines, alkylenediamines, if desired N-alkylated and saturated or unsaturated, cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Mention may be made, by way of examples, of sodium hydroxide, sodium hydride, sodamide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexyiamine, N-Cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1 ,5-diazabicyclo[5.4.0]undec-5-ene (DBU).
The reaction is advantageously carried out at a temperature from approximately 0°C to approximately +150°C, preferably from approximately 20°C to approximately +100°C.
A further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is S, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula l, where Y is O, with a sulfonating agent, preferably P4S10, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
A further subject-matter of the invention is the process for the preparation of the compounds of the formula I, where Y is NRn, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula I, where Y is S, with a compound of formula NHRn, which is known or can be prepared by analogy to relevant known compounds and in which R-u is as defined above in the formula I, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
Salts of compounds I can be prepared in a way known per se. Thus, for example, acid addition salts of compound I are obtained by treatment with a suitable acid or a suitable ion- exchange reagent and salts with bases are obtained by treatment with a suitable base or a suitable ion-exchange reagent.
Salts of compounds I can be converted in the usual way to the free compounds I, acid addition salts, e.g. by treatment with a suitable basic agent or a suitable ion exchange reagent, and salts with bases, e.g. by treatment with a suitable acid or a suitable ion- exchange reagent.
Salts of compounds I can be changed in a way known per se to other salts of compounds I, acid addition salts for example to other acid addition salts, e.g. by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, e.g. with silver acetate, in a suitable solvent, in which an inorganic salt, e.g. silver chloride, being formed is insoluble and for this reason precipitates from the reaction mixture.
According to the method or reaction conditions, the compounds I with salt-forming properties can be obtained in the free form or in the form of salts.
The compounds I can also be obtained in the form of their hydrates and/or can incorporate other solvents, which might, for example, be used in the crystallization of compounds existing in the solid form.
The compounds I can exist in the form of one of the possible isomers or as a mixture of the same, e.g., according to the number, absolute and relative configuration of the asymmetric carbon atoms, as pure isomers, for example optical isomers and/or diastereoisomers, or as mixtures of isomers, such as mixtures of enantiomers, e.g. racemates, mixtures of diastereoisomers or racemate mixtures; the invention relates both to the pure isomers and to all possible mixtures of isomers and is to be correspondingly understood in each case heretofore and hereinafter, even if stereochemical details are not specifically referred to in every case.
Mixtures of diastereoisomers and mixtures of racemates of compounds l obtainable according to the process - depending on the choice of the starting materials and operating methods - or otherwise obtainable can be separated in a known way into the pure diastereoisomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
Correspondingly obtainable mixtures of enantiomers, such as racemates, can be resolved into the optical isomers by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, e.g. high performance liquid chromatography (HPLC) on acetylcellulose, with the help of suitable microorganisms, by cleavage with specific immobilized enzymes, via the formation of inclusion complexes, e.g. by using chiral crown ethers, in which only one enantiomer is complexed.
In addition to through separation of the corresponding mixtures of isomers, pure diastereoisomers or enantiomers according to the invention can also be obtained through generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the invention with educts with correspondingly suitable stereochemistry.
Advantageously, the biologically more effective isomer, e.g. enantiomer, or mixture of isomers, e.g. mixture of enantiomers, is isolated or synthesized each time, provided that the individual components have different biological activity.
In the process of the present invention, use is preferably made of such starting materials and intermediates which result in the compounds I described at the beginning as particularly valuable.
The invention in particular relates to the preparation process described in the example.
Starting materials and intermediates used according to the invention for the preparation of the compounds l which are novel, their use and processes for their preparation likewise form a subject-matter of the invention.The compounds I according to the invention are characterized by a particularly broad activity spectrum and are valuable active ingredients in the field of pest control which are well tolerated by warm-blooded species, fish and plants, including in particular for controlling endo- and ectoparasites which parasitize animals. ln the context of the present invention, the term "ectoparasites" is understood to mean, in particular, insects, mites and ticks. This includes insects of the orders: Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, reference may in particular be made to ectoparasites which are a nuisance to man or animals and which transmit pathogens, for example flies, such as Musca domestica, Musca veiustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia im'tans, and mosquitoes (Nematocera), such as Culicidae, Simuliidae, Psychodidae, but also bloodsucking parasites, for example fleas, such as Ctenocephalides felis and Ctenocephalides caηis (cat and dog fleas), Xenopsylla cheopis, Pulex irriϊans, Dermatophilus penetrans, lice, such as Damalina ovis, Pediculus humanis, stable flies and horse flies (Tabanidae), Haematopota spp., such as Haematopota pluvialis, Tabanidea spp., such as Tabanus nigrovittatus, Chrysopsinaβ spp., such as Chrysops caecutiens, tsetse flies, such as Glossinia species, biting insects, in particular cockroaches, such as Blatella germanica, Blatta orientalis, Periplaneta americana, mites, such as Dermanyssus gallinae, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp., and last but not least ticks. The latter belong to the order Acarina. Known representatives of ticks are, e.g., Boophilυs, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros and the like, which preferably infest warm-blooded animals, including farm animals, such as cows, pigs, sheep and goats, poultry, such as chickens, turkeys and geese, fur-bearing animals, such as mink, foxes, chinchillas, rabbits and the like, and pets, such as cats and dogs, but also man.
The compounds I according to the invention are also effective against all or individual development stages of normally sensitive but also of resistant animal pests, such as insects and representatives of the order Acarina. The insecticidal, ovicidal and/or acaricidal action of the active ingredients according to the invention may in the process be displayed directly, i.e. in killing the pests, which occurs immediately or only after some time, for example during moulting, or their eggs, or indirectly, e.g. in reduced egg laying and/or in a reduced hatching rate, in which the good action corresponds to a kill rate (mortality) of at least 50 to 60%.
The compounds I can also be used against hygiene pests, in particular of the order Diptera with the families Sarcophagidae, Anophilidae and Culicidae; of the orders Orthoptera, Dictyoptera (e.g. the family Blattidae) and Hymenoptera (e.g. the family Formicidae). The compounds I also have lasting activity in the case of phytoparasitic mites and insects. In the case of spider mites of the order Acarina, they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.).
They are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae, Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera, Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders Lepidoptera, Coleoptera, Diptera and Orthoptera.
They are also suitable as soil insecticides against pests in the soil.
The compounds of the formula I are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others.
The compounds of the formula I are also active against plant nematodes of the genera Meloidogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus, Rizoglyphus and others.
The compounds are particularly active against helminths, among which the endoparasitic nematodes and trematodes can be the cause of serious diseases in mammals and poultry, e.g. in sheep, pigs, goats, cattle, horses, donkeys, dogs, cats, guinea pigs and ornamental birds. Typical nematodes of this indication are: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Mention may specifically be made, among the trematodes, of the family of the Fasciolideae, in particular Fasciola hepatica. The particular advantage of the compounds of the formula I is their activity against such parasites, which are resistant to benzimidazole-based active ingredients.
Certain species of the genera Nematodirus, Cooperia and Oesophagostonum attack the intestinal tract of the host animal, while others of the genera Haemonchus and Ostertagia parasitize in the stomach and others of the genus Dictyocaulus parasitize in lung tissue. Parasites of the families Filariidae and Setariidae are found in internal cell tissue and in organs, e.g. the heart, blood vessels, lymph vessels and subcutaneous tissue. Mention may particularly be made here of the dog heartworm, Dirofilaria immitis. The compounds of the formula l are highly effective against these parasites. The pests which can be controlled with the compounds of the formula I also include, from the class Cestoda (tapeworms), the families Mesocestoidae, in particular the genus Mesocestoides, especially M. lineatus; Dilepididae, in particular Dipylidium caninum, Joyeuxiella spp., especially Joyeuxiella pasquali, and Diplopylidium spp.; and Taeniidae, in particular Taenia pisiformis, Taenia cervi, Taenia ovis, Taenia hydatigena, Taenia multiceps, Taenia taeniaeformis, Taenia serialis and Echinocuccus spp., particularly preferably Taenia hydatigena, Taenia ovis, Taenia multiceps, Taenia serialis; Echinocuccus granulosus and Echinococcus granulosus and Echinococcus multilocularis, and Multiceps multiceps.
In a very particularly preferred way, Taenia hydatigena, T. pisiformis, T. ovis, T. taeniaeformis, Multiceps multiceps, Joyeuxiella pasquali, Dipylidium caninum, Mesocestoides spp., Echinococcus granulosus and E. multilocularis are controlled simultaneously with Dirofilaria immitis, Ancylostoma spp., Toxocara spp. and/or Trichuris vulpis on or in dogs and cats. Also in a preferred way, Ctenocephalides felis and/or C.canis are controlled simultaneously with the abovementioned nematodes and cestodes.
The compounds of the formula I are also suitable for controlling parasites which are pathogenic to man, among which may be mentioned, as typical representatives occurring in the digestive tract, those of the genera Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius. The compounds of the present invention are also active against parasites of the genera Wuchereria, Brugia, Onchocerca and Loa from the family of the Filariidae, which occur in the blood, in tissue and in various organs, and also against Dracunculus and parasites of the genera Strongyloides and Trichinella, which specifically infect the gastrointestinal tract.
In addition, the compounds of the formula I are also active against harmful fungi which cause disease in plants and in man and animals.
The good pesticidal action of the compounds of the formula I according to the invention corresponds to a kill rate (mortality) of at least 50-60% of the pests mentioned. In particular, the compounds of the formula I are characterized by an extraordinarily long duration of action.
The compounds of the formula I are used as such or preferably together with the auxiliaries conventional in formulation technology and can accordingly be processed in a known way, for example to emulsifiable concentrates, directly dilutable solutions, dilute emulsions, soluble powders, granules and also encapsulations in polymer substances. The application methods as well as the compositions are chosen in accordance with the intended aims and the prevailing circumstances.
The formulation, i.e. the compositions, preparations or combinations comprising the active ingredient of the formula I, or combinations of these active ingredients with other active ingredients, and, if desired, a solid or liquid additive, is prepared in a known way, for example by intimately mixing and/or grinding the active ingredients with extenders, for example with solvents, solid carriers and, if desired, surface-active compounds (surfactants).
The following are possible as solvents: alcohols, such as ethanol, propanol or butanol, and glycols, and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, isophorone or diacetone alcohol, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide or water, vegetable oils, such as rapeseed oil, castor oil, coconut oil or soybean oil; and, if desired, silicone oils.
Preferred application forms for use in warm-blooded animals for controlling helminths include solutions, emulsions, suspensions (drenches), feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and pour-on formulations, care having to be taken over the physiological compatibility of the formulation auxiliaries.
Suitable binders for tablets and boluses are chemically modified polymeric natural products which are soluble in water or alcohol, such as starch, cellulose or protein derivatives (e.g., methylcellulose, carboxymethylcellulose, ethylhydroxyethylcellulose, proteins, such as zein, gelatin, and the like), and synthetic polymers, for example polyvinyl alcohol, polyvinylpyrrolidone, and the like. Tablets also comprise fillers (e.g., starch, microcrystalline cellulose, sugar, lactose, and the like), lubricants and disintegrating agents.
If the anthelmintic compositions are present in the form of feed concentrates, then high- performance feed, feed cereals or protein concentrates, for example, are used as carriers. Such feed concentrates or compositions can, in addition to the active ingredients, also comprise additives, vitamins, antibiotics, chemotherapeutics, or other pesticides, mainly bacteriostats, fungistats, coccidiostats, or also hormone preparations, anabolics or substances which promote growth, influence the quality of meat from animals for slaughter or are useful to the organism in another way. If the compositions or the active ingredients of the formula I present therein are added directly to the feed or to the drinking water for the animals, the finished feed or the finished drinking water comprises the active ingredients preferably in a concentration from approximately 0.0005 to 0.02% by weight (5-200 ppm). The compounds of the formula I according to the invention can be used alone or in combination with other biocides. They can, e.g., be combined with pesticides possessing the same direction of action, in order to enhance the action, or can be combined with substances possessing another direction of action, in order to broaden the activity spectrum. It may also make sense to add substances which repel, known as repellents. If it is desired to expand the activity spectrum with regard to endoparasites, for example worms, the compounds of the formula I are appropriately combined with substances having endoparasiticidal properties. They can also, naturally, be used in combination with antibacterial compositions. Since the compounds of the formula I represent adulticides, i.e. since they are effective in particular against the adult stages of the target parasites, the addition of pesticides which are more likely to attack the juvenile stages of parasites can be highly advantageous. In this way, most of those parasites causing great economic damage are namely included. In addition, a substantial contribution is also made as well to avoiding the formation of resistance. Some combinations can also lead to synergistic effects, i.e. that the total amount of active substance consumed can be reduced, which is desirable from an ecological viewpoint. Preferred groups of combination participants and particularly preferred combination participants are mentioned subsequently, which combinations can, in addition to a compound of the formula I, comprise one or more of these participants.
Suitable participants in the mixture include biocides, for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellents or detachers.
Nonlimiting examples of suitable insecticides and acaricides are: 1. Abamectin 8. Aiphamethrin 15. Bacillus subtil, toxin 2. AC 303 630 9. Amitraz 16. Bendiocarb 3. Acephate 10. Avermectin B^ 17. Benfuracarb 4. Acrinathrin 11. AZ 60541 18. Bensultap 5. Alanycarb 12. Azinphos E 19. β-Cyfluthrin 6. Aldicarb 13. Azinphos-methyl 20. Bifenthrin 7. α-Cypermethrin 14. Azocyclotin 21. BPMC 22. Brofenprox 55. Dimethoate 88. Formothion
23. Bromophos E 56. Dimethylvinphos 89. Fosthiazate
24. Bufencarb 57. Dioxathion 90. Fubfenprox
25. Buprofezin 58. DPX-MP062 91. HCH
26. Butocarboxim 59. Edifenphos 92. Heptenophos
27. Butylpyridaben 60. Emamectin 93. Hexaflumuron
28. Cadusafos 61. Endosulf an 94. Hexythiazox
29. Carbaryl 62. Esfenvalerate 95. Hydroprene
30. Carbofuran 63. Ethiofencarb 96. Imidacloprid
31. Carbophenothion 64. Ethion 97. Insect-active fungi
32. Cartap 65. Ethofenprox 98. Insect-active
33. Cloethocarb 66. Ethoprophos nematodes
34. Chlorethoxyfos 67. Etrimfos 99. Insect-active viruses
35. Chlorfenapyr 68. Fenamiphos 100. lprobenfos
36. Chlorfluazuron 69. Fenazaquin 01. lsofenphos
37. Chlormephos 70. Fenbutatin oxide 102. Isoprocarb
38. Chlorpyrifos 71. Fenitrothion 103. Isoxathion
39. Gis-Resmethrin 72. Fenobucarb 104. lvermectin
40. Clocythrin 73. Fenothiocarb 105.λ-Cyhalothrin
41. Clofentezine 74. Fenoxycarb 106. Lufenuron
42. Cyanophos 75. Fenpropathrin 107. Malathion
43. Cycloprothrin 76. Fenpyrad 108. Mecarbam
44. Cyfluthrin 77. Fenpyroximate 109. Mesulfenfos
45. Cyhexatin 78. Fenthion HO. Metaldehyde
46. D 2341 79. Fenvalerate 111. Methamidophos
47. Deltamethrin 80. Fipronil 112. Methiocarb
48. Demeton M 81. Fluazinam 113. Methomyl
49. Demeton S 82. Fluazuron 114. Methoprene
50. Demeton-S-methyl 83. Flucycloxυron 115. Metolcarb
51. Dichlofenthion 84. Flucythrinate 116. Mevinphos
52. Dicliphos 85. Flufenoxuron 117. Milbemectin
53. Diethion 86. Flufenprox 118. Moxidectin
54. Diflubenzuron 87. Fonofos 119. Na)ed 120. NC 184 143. Pyraclofos 166. Tetrachlorvinphos 121.N1-25, Acetamiprid 144. Pyridaphenthion 167. Thiafenox 122. Nitenpyram 145. Pyresmethrin 168. Thiodicarb 123.0methoate 146. Pyretnrum 169.Thiofanox 124.0xamyl 147. Pyridaben 170.Thionazin 125. Oxydemeton M 148. Pyrimidif en 171.Thuringiensin 126.0xydeprofos 149. Pyriproxyfen 172.Tralomethrin 127. Parathion 150. RH-5992 173.Triarathene 128. Parathion-m ethyl 151. RH-2485 174.Triazamate 129. Permethrin 152. Salithion 175.Triazophos 130. Phenthoate 153. Sebufos 176.Triazuron 131. Phorate 154. Silaf luof en 177.Trichlorfon 132. Phosalone 155. Spinosad 178.Triflumuron 133. Phosmet l56. Sulfotep 179.Trimethacarb 134. Phoxim 157. Sulprofos 180.Vamidothion 135. Pirimicarb 158.Tebufenozide 181.XMC (3,5-xylyl 136. Pirimiphos E 159.Tebufenpyrad methylcarbamate) 137. Pirimiphos M 160.Tebupirimfos 182.Xylylcarb 138. Promecarb 161.Teflubenzuron 183. Yl 5301/5302 139. Propaphos 162.TefIuthrin 184. ζ-Cypermethrin 140. Propoxur 163.Temephos 185.Zetamethrin 141. Prothiofos 164.Terbam 142. Prothoate 165.Terbufos
Nonlimiting examples of suitable anthelmintics are mentioned subsequently, in which some representatives, in addition to the anthelmintic activity, also have an insecticidal and acaricidal activity and are already included in the above list:
(A1 ) Praziquantel = 2-CyclohexyIcarbonyl-4-oxo-1 ,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1- αjisoquinoline (A2) Closantel = 3,5-Diiodo-N-[5-chloro-2-methyl-4-(α-cyano-4-chlorobenzyl)phenyl]- salicylamide (A3) Triclabendazole = 5-Chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1 H-benzimidazole (A4) Levamisole = -(-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole (A5) Mebendazole = Methyl 5-benzoyl-1 H-benzimidazol-2-yIcarbamate
(A6) Omphalotin = a macrocyclic fermentation product from the fungus Omphalotus olearius disclosed in WO 97/20857 (A7) Abamectin = Avermectin B1 (A8) Ivermectin = 22,23-Dihydroavermectin B1 (A9) Moxidectin = 5-O-Demethyl-28-deoxy-25-(1 ,3-dimethyl-1-butenyl)-6,28-epoxy-23- (methoxyimino)milbe ycin B (A10) Doramectin = 25-Cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)avermectin A1a (A11 ) Milbemectin = Mixture of Milbemycin A3 and Milbemycin A4 (A12) Milbemycin oxime = 5-Oxime of Milbemectin
Nonlimiting examples of suitable repelling substances (repellents or detachers) are:
(RD DEET (N,N-Diethyl-m-toiuamide)
(R2) KBR 3023 N-Butyl-2-oxycarbonyl-2-(2-hydroxyethyl)piperidine
(R3) Cvmiazole = N-2,3-Dihydro-3-methyl-1 ,3-thiazoI-2-ylidene-2,4-xylidine
The participants in the mixture which are mentioned are very well known to a person skilled in the art. Most are described in the various editions of The Pesticide Manual, The British Crop Protection Council, London, others in the various editions of The Merck Index, Merck & Co. Inc., Rahway, New Jersey, USA, or in the patent literature. The following listing is accordingly restricted to a few references by way of examples.
(I) 2-Methyl-2-(methylthio)propionaldehyde Omethylcarbamoyloxime (Aldicarb), from The Pesticide Manual, 11th Ed. (1997), The British Crop Protection Council, London, page 26;
(II) S-(3,4-Dihydro-4-oxobenzo[αfl[1 ,2,3]triazin-3-ylmethyl) 0,0-dimethyl phosphorodithioate (Azinphos-methyl), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 67;
(III) Ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N- isopropyl-β-alaninate (Benfuracarb), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 96;
(IV) 2-Methylbiphenyl-3-ylmethyl (Z)-(1 flS)-c/s-3-(2-chloro-3,3,3-trifluoroprop-1 -enyl)-2,2- dimethylcyclopropanecarboxylate (Bifenthrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 118;
(V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-4-one (Buprofezin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 157; (VI) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (Carbofuran), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 186;
(VII) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl (dibutylaminothio)methylcarbamate (Carbosulfan), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 188;
(VIII) S,S'-(2-Dimethylaminotrimethylene) bis(thiocarbamate) (Cartap), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 193;
(IX) 1-[3,5-Dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-difluorobenzoyl)- urea (Chlorfluazuron), from The Pesticide Manual, 11 Ed. (1997), The British Crop Protection Council, London, page 213;
(X) 0,0-Diethyl 0-3,5,6-trichloro-2-pyridyl phosphorothioate (Chlorpyrifos), from The Pesticide Manual, 11, Ed. (1997), The British Crop Protection Council, London, page 235;
(XI) (/?S)- -Cyano-4-fluoro-3-phenoxybenzyl (1 RS,3RS;1 RS,3RS)-3-(2,2-dicb\orovmy\)-2,2- dimethylcyclopropanecarboxylate (Cyfluthrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 293;
(XII) Mixture of (S)-α-cyano-3-phenoxybenzyl (Z)-(1 fl,3fl)-3-(2-chloro-3,3,3-trifluoro- propenyl)-2,2-dimethylcyclopropanecarboxylate and (ft)-oc-cyano-3-phenoxybenzyl (Z)- (1 S,3S)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (Lambda-Cyhalothrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 300;
(XIII) Racemate consisting of (S)- -cyano-3-phenoxybenzyl (1 ?,3/τ,)-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate and (fl)-α-cyano-3-phenoxybenzyl (1 S,3S)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Alpha-cypermethrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 308;
(XIV) A mixture of the stereoisomers of (S)-α-cyano-3-phenoxybenzyl (1 RS,3RS, RS,3RS)- 3-(2,2-dich!orovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-Cypermethrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 314;
(XV) (S)-α-Cyano-3-phenoxybenzyl (1 ft,3ft)-3-(2,2-dibromovinyl)-2,2~dimethylcyclopropane- carboxylate (Deltamethrin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 344;
(XVI) 1-(4-Chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), from The Pesticide Manual, 11lhEd. (1997), The British Crop Protection Council, London, page 395; (XVII) (1 ,4,5,6,7,7-Hexachloro-8,9,10-trinorbom-5-en-2,3-ylenebismethylene) sulfite (Endosulfan), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 459;
(XVIII) α-Ethylthio-o-tolyl methylcarbamate (Ethiofencarb), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 479;
(XIX) 0,0-Dimethyl O-4-nitro-m-tolyl phosphorothioate (Fenitrothion), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 514;
(XX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 11lhEd. (1997), The British Crop Protection Council, London, page 516;
(XXI) (RS)-α-Cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalerate), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 539;
(XXII) S-[Formyl(methyl)carbamoylmethyl] O.O-dimethyl phosphorodithioate (Formothion), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 625;
(XXIII) 4-Methylthio-3,5-xylyl methylcarbamate (Methiocarb), from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 813;
(XXIV) 7-Chlorobicyclo[3.2.0]hepta-2,6-dien-6-yl dimethyl phosphate (Heptenophos), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 670;
(XXV) 1-(6-Chloro-3-pyridylmethyl)-Λ-nitroimidazolidin-2-ylideneamine (Imidacloprid), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 706;
(XXVI) 2-lsopropylphenyl methylcarbamate (Isoprocarb), from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 729;
(XXVII) 0,S-Dimethyl phosphoramidothioate (Methamidophos), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 808;
(XXVIII) S-Methyl Λ/-(methylcarbamoyloxy)thioacetimidate (Methomyl), from The Pesticide Manual, 11lhEd. (1997), The British Crop Protection Council, London, page 815;
(XXIX) Methyl 3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 844;
(XXX) 0,0-Diethyl O-4-nitrophenyl phosphorothioate (Parathion), from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 926; (XXXI) 0,0-Dimethyl O-4-nitrophenyl phosphorothioate (Parathion-methyl), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 928;
(XXXII) S-6-Chloro-2,3-dihydro-2-oxo-1 ,3-benzoxazol-3-ylmethyl 0,0-diethyl phosphorodithioate (Phosalone), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 963;
(XXXIII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl dimethylcarbamate (Pirimicarb), from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 985;
(XXXIV) 2-lsopropoxyphenyl methylcarbamate (Propoxur), from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 1036;
(XXXV) 1 -(3,5-Dichloro-2,4-dif luorophenyl)-3-(2,6-dif luorobenzoyl)urea (Tef lubenzuron), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1158;
(XXXVI) S-tert-Butylthiomethyl < ,0-diethyl phosphorodithioate (Terbufos), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1165;
(XXXVII) Ethyl (3-tert-butyl-1 -dimethylcarbamoyl-1 H-1 ,2,4-triazol-5-ylthio)acetate, (Triazamate), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1224;
(XXXVIU) Aba ectin, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 3; (XXXIX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 516; (XL) /V-feA -Butyl-/V-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (Tebufenozide), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1147; (XLI) (+)-5-Amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole- 3-carbonitrile (Fipronil), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 545; (XLII) (flS)-α-Cyano-4-fluoro-3-phenoxybenzyl (1 RS,3RS;-\ HS,3SfiJ-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate (beta-Cyfluthrin), from The Pesticide Manual, 11lhEd. (1997), The British Crop Protection Council, London, page 295; (XLIII) (4-Ethoxyphenyl)[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (Silafluofen), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1105; (XLIV) tert-Butyl (E)-α-(1 ,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate (Fenpyroximate), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 530; (XLV) 2-fert-Butyl-5-(4-ferf-butylbenzylthio)-4-chloropyridazin-3(2H)-one (Pyridaben), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1161; (XLVI) 4-[[4-(1 ,1-Dimethylethyl)phenyl]ethoxy]quinazoline (Fenazaquin), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 507; (XLVII) 4-Phenoxyphenyl (f?S)-2-(2-pyridyioxy)propyl ether (Pyriproxyfen), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1073; (XLVIII) 5-Chloro-Λ-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidin-4- amine (Pyrimidifen), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1070; (XLIX) (E)-A/-(6-Chloro-3-pyridylmethyl)-A-ethyl-yV-methyl-2-nitrovinylidenediamine (Nitenpyram), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 880; (L) (£)-Λ/1-[(6-Chloro-3-pyridyl)methyl]-Λ -cyano-Λ/1 -methylacetamidine (Nl-25, Acetamiprid), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 9; (LI) Avermectin B1 ; from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 3; (Lll) An insect-active extract from a plant, in particular (2R,6aS,12aS)-1 ,2,6,6a,12,12a- hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4- ?]furo[2,3-/i]chromen-6-one (Rotenone), from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1097; and an extract from Azadirachta indica, in particular azadirachtin, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 59; (Llll) A preparation comprising insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 671 ; Steinemema feltiae, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1115, and Steinernema scapterisci, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1116;
(LIV) A preparation obtainable from Bacillus subtilis, from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 72; or from a Bacillus thuringiensis strain except for compounds isolated from GC91 or from NCTC11821 ; The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 73;
(LV) A preparation comprising insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 1266; Beauveήa brogniartii, from The Pesticide Manual, 11,hEd. (1997), The British Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 83;
(LVI) A preparation comprising insect-active viruses, preferably Neodipridon Sertifer NPV, from The Pesticide Manual, 11lhEd. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus, from The Pesticide Manual, 11thEd. (1997), The British Crop Protection Council, London, page 291 ; (CLXXXI) Λ/'-tert-Butyl-Λ/-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH- 2485, Methoxyfenozide), from The Pesticide Manual, 11 hEd. (1997), The British Crop Protection Council, London, page 1094;
(CLXXXII) Isopropyl Λ/'-[4-methoxybiphenyl-3-yl]hydrazinecarboxylate (D 2341), from Brighton Crop Protection Conference, 1996, 487- 493; and
(R2) Book of Abstracts, 212th ACS National Meeting, Orlando, FL, August 25-29 (1996), AGRO-020. Publisher: American Chemical Society, Washington, D.C. CONEN: 63BFAF.
As a consequence of the above details, a further essential aspect of the present invention relates to combination preparations for the control of parasites on warm-blooded animals, characterised in that they contain, in addition to a compound of formula I, at least one further active ingredient having the same or different sphere of activity and at least one physiologically acceptable carrier. The present invention is not restricted to two-fold combinations.
Especially preferred combination partners for the compounds of the formula I of the present inventions are the more modern natural or chemically modified macrocyclic lactones (macrolides), such as avermectins, milbemycins and derivatives thereof, including prominent representatives such as Ivermectin, Doramectin, Moxidectin, Selamectin, Emamectin, Eprinomectin, Milbemectin, Abamectin, Milbemycin oxime, Nemadectin, and a derivative thereof, in the free form or in the form of a physiologically acceptable salt.
The combination of these two different classes of compounds leads to several advantageous effects. In the first instant, one observes a broadening of the activity spectrum with regard to the endo-parasites. The combination product is highly active against all sorts of commercially important worms and, what is really surprising, also against metabolic active larval stages. Investigations concerning arrested larval stages are still ongoing but it could well turn out that the combination product will also be effective against these stages.
A further advantage of the combination product is the pest resistance management, meaning that the occurrence of resistance against the compounds of the formula I can drastically be delayed by the administration of the combination product instead of applying the compounds of formula I only. Another advantage is that the combination product can successfully be used even in those cases where the worm population has already developed resistance against a macrocyclic lactones.
Beyond this, a major advantage of the compounds of the formula 1 is their exhibiting full efficacy against worms resistant to commonly used products such as representatives of the macrocyclic lactones, e.g. Ivermectin or Moxidectin, and to Levamisole or representatives of the benzimidazole class of anthelmintics.
The macrocyclic lactones are most preferred because they exhibit a broad spectrum of activity. Most of them exhibit ecto- and in parallel endo-parsiticidal activity. Therefore, they are also called endectocides. Macrocyclic lactones bind to gluta ated chlorine channels causing paralysis of the parasites in the first instance, followed by their death.
In the context of the invention, a preferred group of macrocyclic lactones is represented by compounds of formula
Figure imgf000030_0001
wherein X is -C(H)(OH)- ; -C(O)- ; or -C(=N-OH)-; Y is -C(H2)- ; =C(H)- ; -C(H)(OH)- ; or ■ C(=N-OCH3)-; Ri is hydrogen or one of radicals
Figure imgf000030_0002
R4 is hydroxyl, -NH-CH3 or -NH-OCH3; R2 is hydrogen, -CH3, -C2H5, -CH(CH3)-CH3, - CH(CH3)-C2H5, -C(CH3)=CH-CH(CH3)2 or cyclohexyl; and if the bond between atoms 22 and 23 represents a double bond the carbon atom in 23-position is unsubstituted so that Y is =C(H)-, or if is the bond between atoms 22 and 23 is a single bond the carbon atom in 23- position is unsubstituted or substituted by hydroxy or by the group =N-0-CH3 so that Y is - C(H2)-; -C(H)(OH)- ; or -C(=N-OCH3)-; in free form or in the form of a physiologically acceptable salt.
Typical and especially preferred representatives of compounds of formula A are:
1 ) Ivermectin is 22,23-Dihydroabamectin; 22,23-dihydroavermectin B1 ; or 22,23-dihydro-C- 076B1 , wherein X is -C(H)(OH)- ; Y is -C(H2)-; R1 is the radical
Figure imgf000030_0003
R2 is either -CH(CH3)-CH3 or -CH(CH3)-C2H5 and the bond between atoms 22 and 23 represents a single bond. Ivermectin is known from US-4,199,569.
2) Doramectin is 25-Cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)avermectin A1a, wherein X is -C(H)(OH)- ; Y is =C(H)-; R is the radical
Figure imgf000031_0001
R2 is cyclohexyl and the bond between atoms 22 and 23 represents a double bond. Doramectin is known from US-5,089,480.
3) Moxidectin, is [6R ,23E, 25S (E)]-5-O-Demethyl-28-deoxy-25-(1 ,3-dimethyl-1-butenyl)- 6,28-epoxy-23-(methoxyimino)milbemycin B, wherein X is -C(H)(OH)- ; Y is -C(=N-OCH3)-; Ri is hydrogen; R2 is -C(CH3)=CH-CH(CH3)2; and the bond between atoms 22 and 23 represents a single bond. Moxidectin is known from EP-0,237,339 and US-4,916,154.
4) Selamectin is 25-cyclohexyl-25-de(1 -methylpropyl)-5-deoxy-22,23-dihydro-5-
(hydroxyimino)avermectin B1 monosaccharide and thus a compound of formula A, wherein
X is -C(=N-OH)-; Y is -C(H2)-; ^ is the radical
Figure imgf000031_0002
R2 is cyclohexyl; and the bond between atoms 22 and 23 represents a single bond. Selamectin is known e.g. from: ECTOPARASITE ACTIVITY OF SELAMECTIN; A novel endectocide for dogs and cats. A Pfizer Symposium, held in conjunction with The 17th international Conference of the World Association for the Advancement of Veterinary Parasitology, 19 August 1999. Copenhagen, Denmark.
5) Emamectin is (4"-R )-5-O-demethyl-4"-deoxy-4"-(methylamino)avermectin A1 a and (4"- R)-5-0-demethyl-25-de(1-methylpropyl)-4"-deoxy-4"-(methylamino)-25-(1 - methylethyl)avermectin A1a (9:1), wherein X is -C(H)(OH)- ; Y is =C(H)- ; Ri is
Figure imgf000032_0001
R2 is -CH(CH3)-CH3, or -CH(CH3)-C2H5, and the bond between atoms 22 and 23 represents a double bond. Emamectin is known from US-4,874,749.
6) Eprinomectin is (4"-R )-4"-epi-(acetylamino)-4"-deoxyavermectin B1 , wherein X is - C(H)(OH)- ; Y is =C(H)- ; R is the radical
Figure imgf000032_0002
R2 is -CH(CH3)-CH3, or -CH(CH3)-C2H5, and the bond between atoms 22 and 23 represents a double bond. Eprinomectin is known from US-4,427,663.
7) Milbemectin is (6R,25R)-5-0-demethyl-28-deoxy-6,28-epoxy-25-methylmilbemycin, wherein X is -C(H)(OH)- ; Y is -C(H2)-; is hydrogen; R2 is -CH3, or -C2H5; and the bond between atoms 22 and 23 represents a single bond. Milbemectin is known from US- 3,950,360.
8) Abamectin is Avermectin B1 which is also named 5-O-demethylavermectin A1 a and 5-0- demethyl-25-de(1-methylpropyl)-25-(1-methylethyl)avermectin A1 a (4:1), wherein X is - C(H)(OH)- ; Y is =C(H)- ; R^ is the radical
Figure imgf000032_0003
R2 is -CH(CH3)-CH3, or -CH(CH3)-C2H5; and the bond between atoms 22 and 23 represents a double bond. Abamectin is known from US-4,310,519.
9) Milbemycin oxi is milbemycin A4 5-oxime; milbemycin A3 5-oxime, wherein X is - C(H)(OH)- ; Y is -C(H2)-; R is hydrogen; R2 is -CH(CH3)-CH3, or -CH(CH3)-C2H5, and the bond between atoms 22 and 23 represents a single bond. Milbemycin oxim is known from US-4,547,520.
10) The compound of the formula A wherein X is -C(H)(OH)- ; Y is -C(H2)-; ^ is the radical
Figure imgf000033_0001
R2 is -CH3 or C2H5, and the bond between atoms 22 and 23 represents a single bond. This compound is known from WO 01/83500.
11) Nemadectin is antibiotic S-541A; also named [6 R, 23S, 25S, (E) ]-5-0-Demethyl-28- deoxy-25-(1 ,3-dimethyl-1-butenyl)-6,28-epoxy-23-hydroxymilbemycin B; wherein X is =CH- OH; Y is -C(H2)- ; R^ is hydrogen; R2 is -C(CH3)=CH-CH(CH3)2, and the bond between atoms 22 and 23 represents a single bond. Nemadectin is known from US-4,869,901.
The compounds specifically mentioned under items 1-11 hereinbefore are preferred embodiments of the present invention and can be used either alone or in combination with another endo-parasiticide, ecto-parasiticide or endecticide.
Especially preferred combination partners are Ivermectin, Abamectin and Moxidectin.
The anthelmintic compositions according to the invention generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of active ingredient of the formula I or mixtures thereof, and 99.9 to 1% by weight, in particular 99.8 to 5% by weight, of a solid or liquid additive, including 0 to 25% by weight, in particular 0.1 to 25% by weight, of a surfactant.
The compositions according to the invention can be applied topically, perorally, parenterally or subcutaneously to the animals to be treated, the compositions being present in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses, capsules and as pour-on formulations.
The pour-on or spot-on method consists in applying the compound of the formula I to a locally restricted part of the skin or fur, advantageously on the neck or back of the animal. This is carried out, e.g., by applying a spot or dash of the pour-on or spot-on formulation to a relatively small area of the fur, from where the active substance spreads out virtually unaided over wide regions of the fur because of the spreading components of the formulation and supported by the movements of the animal. lt is advantageous for pour-on or spot-on formulations to comprise carriers which promote speedy distribution on the surface of the skin or in the fur of the host animal and which are generally described as spreading oils. Suitable carriers are, e.g., oily solutions; alcoholic and isopropanolic solutions, for example solutions of 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxal ester, oleyl oleate, decyl oleate, hexyl laurate, capric acid esters of saturated fatty alcohols with a chain length of Cι2-Cι8; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, diisopropyl adipate or di(n-butyl) adipate, or also solutions of esters of aliphatic acids, e.g. glycols. It can be advantageous if a dispersant known from the pharmaceutical or cosmetics industry is additionally present. Examples are 2-pyrrolidone, 2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and ethers and esters thereof, propylene glycol or synthetic triglycerides.
The oily solutions include, e.g., vegetable oils, such as olive oil, groundnut oil, sesame oil, pine oil, linseed oil or castor oil. The vegetable oils can also be present in epoxidized form. Paraffin oils and silicone oils can also be used.
In general, a pour-on or spot-on formulation comprises 1 to 20% by weight of a compound of the formula I, 0.1 to 50% by weight of dispersant and 45 to 98.9% by weight of solvent.
The pour-on or spot-on method can be used particularly advantageously with gregarious animals, such as cattle, horses, sheep or pigs, where it is difficult or time-consuming to treat all the animals orally or via injection. Because of its simplicity, this method can naturally also be used with all other animals, including individual domestic animals or pets, and is very popular with animal owners because it can often be implemented without the expert assistance of a veterinary surgeon.
While concentrated compositions are more preferred as commercially available products, the end user generally uses dilute compositions.
Such compositions can comprise yet further additives, such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects.
Such anthelmintic compositions used by the end user likewise form part of the present invention.
In each of the methods according to the invention for controlling pests or of the pesticides according to the invention, the active ingredients of the formula I can be used in all their steric configurations or mixtures thereof.
The invention also includes a method for the prophylactic protection of warm-blooded animals, in particular of productive livestock, domestic animals and pets, against parasitic helminths, which comprises applying the active ingredients of the formula I or the active ingredient formulations prepared therefrom as a feed additive or drinking water additive or also in the solid or liquid form, orally, by injection or parenterally, to the animals. The invention also includes the compounds of the formula 1 according to the invention for use in one of the methods mentioned.
The following examples serve merely to illustrate the invention, without limiting it, the term "active ingredient" representing a substance listed in Table 1.
Preferred formulations are in particular composed in the following way:
(% = per cent by weight)
Formulation examples
1. Granules a) b)
Active ingredient 5% 10%
Kaolin 94% -
Highly dispersed silica 1% -
Attapulgite - 90%
The active ingredient is dissolved in methylene chloride and sprayed onto the carrier, and the solvent is subsequently evaporated under reduced pressure. Such granules can be added to the animal feed.
2. Granules
Active ingredient 3%
Polyethylene glycol (MW 200) 3%
Kaolin 94%
(MW = molecular weight)
The finely milled active ingredient is applied evenly in a mixer to the kaolin, which has been moistened with polyethylene glycol. In this way, dust-free coated granules are obtained.
3. Tablets or Boluses I Active ingredient 33.00% Methylcellulose 0.80% Highly dispersed silica 0.80% Maize starch 8.40% II Cryst. lactose 22.50% Maize starch 17.00% Microcryst. cellulose 16.50% Magnesium stearate 1.00% I Methylcellulose is stirred into water. After the material has swollen, silica is stirred in and the mixture is homogeneously suspended. Active ingredient and maize starch are mixed. The aqueous suspension is incorporated in this mixture and kneaded to a dough. The substance thus obtained is granulated through a 12 M sieve and dried. II All 4 auxiliaries are intimately mixed. III The premixes obtained according to I and II are mixed and pressed to give tablets or boluses.
4. Iniectables A. Oilv vehicle (slow release) 1. Active ingredient 0.1-1.0 g Groundnut oil ad 100 ml 2. Active ingredient 0.1-1.0 g Sesame oil ad 100 ml
Preparation: The active ingredient is dissolved in a portion of the oil with stirring and, if desired, gentle heating, made up to the required volume after cooling and sterilely filtered through a suitable membrane filter with a size of 0.22 μm. B. Water-miscible solvent (medium release rate) 1. Active ingredient 0.1-1.0 g 4-Hydroxymethyl-1 ,3-dioxolane (glycerol formal) 40 g 1 ,2-Propanediol ad 100 ml 2. Active ingredient 0.1-1.0 g Glycerol dimethyl acetal 40 g 1 ,2-Propanediol ad 100 ml
Preparation: The active ingredient is dissolved in a portion of the solvent with stirring, made up to the required volume and sterilely filtered through a suitable membrane filter with a size of 0.22 μm. C. Aqueous solubilisate (rapid release) 1. Active ingredient 0.1-1.0 g Polyethoxylated castor oil (40 ethylene oxide units) 10 g 1 ,2-Propanediol 20 g Benzyl alcohol 1 g Water for injections ad 100 ml 2. Active ingredient 0.1-1.0 g Polyethoxylated sorbitan monooleate (20 ethylene oxide units) 8 g 4-Hydroxymethyl-1 ,3-dioxolane (glycerol formal) 20 g Benzyl alcohol 1 g Water for injections ad 100 ml
Preparation: The active ingredient is dissolved in the solvents and the surfactant and made up to the required volume with water. Sterile filtration is carried out through a suitable membrane filter with a pore diameter of 0.22 μm.
5. Pour-on
A.
Active ingredient 5 g
Isopropyl myristate 10 g
Isopropanol ad 100 ml
B.
Active ingredient 2 g
Hexyl laurate 5 g
Triglycerides of medium chain length 15 g Ethanol ad 100 ml
C.
Active ingredient 2 g
Oleyl oleate 5 g
N-Methylpyrro!idone 40 g
Isopropanol ad 100 ml
The aqueous systems can preferably also be used for oral and/or intraruminal administration.
The compositions can also comprise further additives, such as stabilizers, e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil), antifoaming agents, e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects.
Further biologically active substances or additives which are neutral towards the compounds of the formula I and have no adverse effect on the host animal to be treated, and mineral salts or vitamins, can also be added to the compositions described.
The following examples serve to clarify the invention. They do not limit the invention. The symbol 'h' denotes hour.
Preparation examples
Example 1 : 4-l2-cvano-2-(4-trifluoromethoχybenzoylamino)-1 -propoxyl-3- trifluoromethylbenzamide
Figure imgf000038_0001
a) In 30 ml of tetrahydrofuran 1.13 g of 4-fluoro-3-trifluoromethylbenzonitrile and 1.87 g of (2-methyl-2-hydoxymethyl-[1 ,3]dioxolan are diluted and cooled to 0°C. Then a cold solution of 0.73 g potassium t-butoxide in tetrahydrofuran is added dropwise. After stirring for 30 min at 0°C the reaction mixture is diluted with 50 ml of ethyl acetate and washed twice with a saturated solution of ammonium chloride, water and brine. The organic phase is finally dried over magnesium sulfate, filtered and concentrated under vacuum. The residue is then stirred with hexane, filtered and dried to yield amorphous crystals of 4-(2-methyl-[1 ,3]dioxolan-2- ylmethoxy])-3-trifluoromethylbenzonitrile. b) In 30 ml of ethylene glycol and 25 ml of an 8N aqueous solution of potassium hydroxide 862 mg of 4-(2-methyl-[1 ,3]dioxolan-2-ylmethoxy])-3-trifluoromethylbenzonitrile are dissolved and stirred for 22 h at 65°C. The yellow mixture is then cooled to 0°C, neutralized with an aqueous solution of 2N hydrochloric acid, diluted with 50 ml of ethyl acetate and washed with water and brine. The organic phases are dried over magnesium sulfate, filtered and evaporated to afford crude 4-(2-methyl-[1 ,3]dioxolan-2-ylmethoxy])-3-trifluoromethylbenz- amide. c) In 15 ml of acetone and 7.5 ml of an aqueous solution of 2N hydrochloric acid 916 mg of crude 4-(2-methyl-[1 ,3]dioxo!an-2-ylmethoxy])-3-trifluoromethylbenzarnide are dissolved, stirred at reflux temperature for 24 h, then cooled to room temperature and evaporated. The residue is diluted in 30 ml ethyl acetate and washed with a saturated solution of sodium carbonate and water. After separation the organic phase is dried over magnesium sulfate, filtered and evaporated to yield 4-(2-oxopropoxy)-3-trifluoromethylbenzamide. d) In 5 ml of ethanol 260 mg of 4-(2-oxopropoxy)-3-trifluoromethylbenzamide is dissolved, then 73.5 mg of sodium cyanide, 80.2 mg of ammonium chloride and 15 ml of an aqueous solution of 25% ammonia is added and the mixture stirred for 24 h at room temperature. After evaporation of the solvent the residue is re-dissolved and stirred in ethyl acetate, dried with magnesium sulfate, filtered and evaporated to afford 4-(2-amino-2-cyanopropoxy)-3- trifluoromethylbenza ide. e) In 4 ml of dichloromethane 171 mg of 4-(2-amino-2-cyanopropoxy)-3-trifluoromethylbenz- amide are dissolved, then 108 mg of ethyldiisopropylamine and 160 mg of 4-(trifluoro- methoxy)-benzoylchloride are added. The mixture is stirred overnight at room temperature, then diluted with 30 ml of dichloromethane and successively washed with a saturated aqueous solution of sodium bicarbonate, water, an aqueous solution of 1 N hydrochloric acid and finally brine. The organic phases are dried over magnesium sulfate, filtered and evaporated. The crude residue is purified by flash chromatography to yield the title compound.
The substances mentioned in the following table can also be prepared analogously to the procedure described above. The melting point values are given in °C.
Table l
Figure imgf000040_0001
No. R7 Ra Ra io Phys. data
1.1 4'-COOH H H H
1.2 4'-COOH H 4-F H
1.3 4'-COOH H 4-CI H
1.4 4'-COOH H 4-CN H
1.5 4'-COOH H 4-CH3 H
1.6 4'-COOH H 4-CF3 H
1.7 4'-COOH H 4-OCF3 H
1.8 4'-COOH H 4-SCF3 H
1.9 4'-COOH H 4-S(0)CF3 H
1.10 4'-COOH H 4-S(0)2CF3 H
1.11 4'-COOH H 2-F H
1.12 4'-COOH H 2-CI H
1.13 4'-COOH H 2-CN H
1.14 4'-COOH H 2-CH3 H
1.15 4'-COOH H 2-CF3 H
1.16 4'-COOH H 2-0CF3 H
1.17 4'-COOH H 2-SCF3 H
1.18 4'-COOH H 2-S(0)CF3 H
1.19 4'-COOH H 2-S(0)2CF3 H
1.20 4'-COOH H H 4-NH2
1.21 4'-COOH H H 4-COOH
1.22 4'-COOH H H 4-CONH2
1.23 4'-COOH H H 4-CSNH2
1.24 4'-COOH H H 4-NHCONH2
1.25 4'-COOH H H 4-NHCSNH2
1.26 4'-COOH H H 4-OCSNH2 1.27 4'-COOH H H 3-OC(F2)0-4
1.28 4'-COOH H H 3-SC(F2)S-4
1.29 4'-COOH H 2-F 4-NH2
1.30 4'-COOH H 2-CI 4-COOH
1.31 4'-COOH H 2-CN 4-CONH2
1.32 4'-COOH H 2-CH3 4-CSNH2
1.33 4'-COOH H 2-CF3 4-NHCONH2
1.34 4'-COOH H 2-OCF3 4-NHCSNH2
1.35 4'-COOH H 2-SCF3 4-OCSNH2
1.36 4'-COOH 2'-CN H H
1.37 4'-COOH 2'-CN 4-F H
1.38 4'-COOH 2'-CN 4-CI H
1.39 4'-COOH 2'-CN 4-CN H
1.40 4'-COOH 2'-CN 4-CH3 H
1.41 4'-COOH 2'-CN 4-CF3 H
1.42 " 4'-COOH 2'-CN 4-OCF3 H
1.43 4'-COOH 2'-CN 4-SCF3 H
1.44 4'-COOH 2'-CN 4-S(0)CF3 H
1.45 4'-COOH 2'-CN 4-S(0)2CF3 H
1.46 4'-COOH 2'-CN 2-F H
1.47 4'-COOH 2'-CN 2-CI H
1.48 4'-COOH 2'-CN 2-CN H
1.49 4'-COOH 2'-CN 2-CH3 H
1.50 4'-COOH 2'-CN 2-CF3 H
1.51 4'-COOH 2'-CN 2-OCF3 H
1.52 4'-COOH 2'-CN 2-SCF3 H
1.53 4'-COOH 2'-CN 2-S(0)CF3 H
1.54 4'-COOH 2'-CN 2-S(0)2CF3 H
1.55 4'-COOH 2'-CN H 4-NH2
1.56 4'-COOH 2'-CN H 4-COOH
1.57 4'-COOH 2'-CN H 4-CONH2
1.58 4'-COOH 2'-CN H 4-CSNH2
1.59 4'-COOH 2'-CN H 4-NHCONH2
1.60 4'-COOH 2'-CN H 4-NHCSNH2 1.61 4'-COOH 2'-CN H 4-OCSNH2
1.62 4'-COOH 2'-CN H 3-OC(F2)0-4
1.63 4'-COOH 2'-CN H 3-SC(F2)S-4
1.64 4'-COOH 2'-CN 2-F 4-NH2
1.65 4'-COOH 2'-CN 2-CI 4-COOH
1.66 4'-COOH 2'-CN 2-CN 4-CONH2
1.67 4'-COOH 2'-CN 2-CH3 4-CSNH2
1.68 4'-COOH 2'-CN 2-CF3 4-NHCONH2
1.69 4'-COOH 2'-CN 2-OCF3 4-NHCSNH2
1.70 4'-COOH 2'-CN 2-SCF3 4-OCSNH2
1.71 4'-COOH 2'-CH3 H H
1.72 4'-COOH 2'-CH3 4-F H
1.73 4'-COOH 2'-CH3 4-CI H
1.74 4'-COOH 2'-CH3 4-CN H
1.75 4'-COOH 2'-CH3 4-CH3 H
1.76 4'-COOH 2'-CH3 4-CF3 H
1.77 4'-COOH 2'-CH3 4-OCF3 H
1.78 4'-COOH 2'-CH3 4-SCF3 H
1.79 4'-COOH 2'-CH3 4-S(0)CF3 H
1.80 4'-COOH 2'-CH3 4-S(0)2CF3 H
1.81 4'-COOH 2'-CH3 2-F H
1.82 4'-COOH 2'-CH3 2-CI H
1.83 4'-COOH 2'-CH3 2-CN H
1.84 4'-COOH 2'-CH3 2-CH3 H
1.85 4'-COOH 2'-CH3 2-CF3 H
1.86 4'-COOH 2'-CH3 2-OCF3 H
1.87 4'-COOH 2'-CH3 2-SCF3 H
1.88 4'-COOH 2'-CH3 2-S(0)CF3 H
1.89 4'-COOH 2'-CH3 2-S(0)2CF3 H
1.90 4'-COOH 2'-CH3 H 4-NH2
1.91 4'-COOH 2'-CH3 H 4-COOH
1.92 4'-COOH 2'-CH3 H 4-CONH2
1.93 4'-COOH 2'-CH3 H 4-CSNH2
1.94 4'-COOH 2'-CH3 H 4-NHCONH2 1.95 4'-COOH 2'-CH3 H 4-NHCSNH2
1.96 4'-COOH 2'-CH3 H 4-OCSNH2
1.97 4'-COOH 2'-CH3 H 3-OC(F2)0-4
1.98 4'-COOH 2'-CH3 H 3-SC(F2)S-4
1.99 4'-COOH 2'-CH3 2-F 4-NH2
1.100 4'-COOH 2'-CH3 2-CI 4-COOH
1.101 4'-COOH 2'-CH3 2-CN 4-CONH2
1.102 4'-COOH 2'-CH3 2-CH3 4-CSNH2
1.103 4'-COOH 2'-CH3 2-CF3 4-NHCONH2
1.104 4'-COOH 2'-CH3 2-OCF3 4-NHCSNH2
1.105 4'-COOH 2'-CH3 2-SCF3 4-OCSNH2
1.106 4'-COOH 2'-CF3 H H
1.107 4'-COOH 2'-CF3 4-F H
1.108 4'-COOH 2'-CF3 4-CI H
1.109 4'-COOH 2'-CF3 4-CN H
1.110 4'-COOH 2'-CF3 4-CH3 H
1.111 4'-COOH 2'-CF3 4-CF3 H
1.112 4'-COOH 2'-CF3 4-OCF3 H m.p. 110-4°
1.113 4'-COOH 2'-CF3 4-SCF3 H
1.114 4'-COOH 2'-CF3 4-S(0)CF3 H
1.115 4'-COOH 2'-CF3 4-S(0)2CF3 H
1.116 4'-COOH 2'-CF3 2-F H
1.117 4'-COOH 2'-CF3 2-CI H
1.118 4'-COOH 2'-CF3 2-CN H
1.119 4'-COOH 2'-CF3 2-CH3 H
1.120 4'-COOH 2'-CF3 2-CF3 H
1.121 4'-COOH 2'-CF3 2-0CF3 H
1.122 4'-COOH 2'-CF3 2-SCF3 H
1.123 4'-COOH 2'-CF3 2-S(0)CF3 H
1.124 4'-COOH 2'-CF3 2-S(0)2CF3 H
1.125 4'-COOH 2'-CF3 H 4-NH2
1.126 4'-COOH 2'-CF3 H 4-COOH
1.127 4'-COOH 2'-CF3 H 4-CONH2
1.128 4'-COOH 2'-CF3 H 4-CSNH2 1.129 4'-COOH 2'-CF3 H 4-NHCONH2
1.130 4'-COOH 2'-CF3 H 4-NHCSNH2
1.131 4'-COOH 2'-CF3 H 4-OCSNH2
1.132 4'-COOH 2'-CF3 H 3-OC(F2)0-4
1.133 4'-COOH 2'-CF3 H 3-SC(F2)S-4
1.134 4'-COOH 2'-CF3 2-F 4-NH2
1.135 4'-COOH 2'-CF3 2-CI 4-COOH
1.136 4'-COOH 2'-CF3 2-CN 4-CONH2
1.137 4'-COOH 2'-CF3 2-CH3 4-CSNH2
1.138 4'-COOH 2'-CF3 2-CF3 4-NHCONH2
1.139 4'-COOH 2'-CF3 2-OCF3 4-NHCSNH2
1.140 4'-COOH 2'-CF3 2-SCF3 4-OCSNH2
1.141 4'-COOH 2'-OCF3 H H
1.142 4'-COOH 2'-OCF3 4-F H
1.143 4'-COOH 2'-OCF3 4-CI H
1.144 4'-COOH 2'-OCF3 4-CN H
1.145 4'-COOH 2'-OCF3 4-CH3 H
1.146 4'-COOH 2'-OCF3 4-CF3 H
1.147 4'-COOH 2'-OCF3 4-OCF3 H
1.148 4'-COOH 2'-OCF3 4-SCF3 H
1.149 4'-COOH 2'-OCF3 4-S(0)CF3 H
1.150 4'-COOH 2'-OCF3 4-S(0)2CF3 H
1.151 4'-COOH 2'-OCF3 2-F H
1.152 4'-COOH 2'-OCF3 2-CI H
1.153 4'-COOH 2'-OCF3 2-CN H
1.154 4'-COOH 2'-OCF3 2-CH3 H
1.155 4'-COOH 2'-OCF3 2-CF3 H
1.156 4'-COOH 2'-OCF3 2-OCF3 H
1.157 4'-COOH 2'-OCF3 2-SCF3 H
1.158 4'-COOH 2'-OCF3 2-S(0)CF3 H
1.159 4'-COOH 2'-OCF3 2-S(0)2CF3 H
1.160 4'-COOH 2'-OCF3 H 4-NH2
1.161 4'-COOH 2'-OCF3 H 4-COOH
1.162 4'-COOH 2'-OCF3 H 4-CONH2 1 .163 4'-COOH 2'-OCF3 H 4-CSNH2
1.164 4'-COOH 2'-OCF3 H 4-NHCONH2
1.165 4'-COOH 2'-OCF3 H 4-NHCSNH2
1.166 4'-COOH 2'-OCF3 H 4-OCSNH2
1.167 4'-COOH 2'-OCF3 H 3-OC(F2)0-4
1.168 4'-COOH 2'-OCF3 H 3-SC(F2)S-4
1.169 4'-COOH 2'-OCF3 2-F 4-NH2
1.170 4'-COOH 2'-OCF3 2-CI 4-COOH
1.171 4'-COOH 2'-OCF3 2-CN 4-CONH2
1.172 4'-COOH 2'-OCF3 2-CH3 4-CSNH2
1.173 4'-COOH 2'-OCF3 2-CF3 4-NHCONH2
1.174 4'-COOH 2'-OCF3 2-OCF3 4-NHCSNH2
1.175 4'-COOH 2'-OCF3 2-SCF3 4-OCSNH2
1.176 4'-COOH 2'-CeH5 H H
1 .177 4'-COOH 2'-C6H5 4-F H
1.178 4'-COOH 2'-C6H5 4-CI H
1.179 4'-COOH 2'-C8H5 4-CN H
1.180 4'-COOH 2'-C6H5 4-CH3 H
1.181 4'-COOH 2'-C6H5 4-CF3 H
1.182 4'-COOH 2'-C6H5 4-OCF3 H
1.183 4'-COOH 2'-C6H5 4-SCF3 H
1.184 4'-COOH 2'-C6Hδ 4-S(0)CF3 H
1.185 4'-COOH 2'-C6H5 4-S(0)2CF3 H
1.186 4'-COOH 2'-C6H5 2-F H
1.187 4'-COOH 2'-C6H5 2-CI H
1.188 4'-COOH 2'-C6H5 2-CN H
1.189 4'-COOH 2'-C6H5 2-CH3 H
1.190 4'-COOH 2'-C6H5 2-CF3 H
1.191 4'-COOH 2'-C6H5 2-OCF3 H
1.192 4'-COOH 2'-C6H5 2-SCFg H
1.193 4'-COOH 2'-C6H5 2-S(0)CF3 H
1.194 4'-COOH 2'-C6H5 2-S(0)2CF3 H
1.195 4!-COOH 2'-C6H5 H 4-NH2
1.196 4'-COOH 2'-C6H5 _ H 4-COOH 1.197 4'-COOH 2'-C6H5 H 4-CONH2 1.198 4'-COOH 2'-CeH5 H 4-CSNH2 1.199 4'-COOH 2'-C6H5 H 4-NHCONH2 1.200 4'-COOH 2'-C6H5 H 4-NHCSNH2 1.201 4'-COOH '-CeH5 H 4-OCSNH2 1.202 4'-COOH 2'-C6H5 H 3-OC(F2)0-4 1.203 4'-COOH 2'-C6Hδ H 3-SC(F2)S-4 1.204 4'-COOH 2'-C6H5 2-F 4-NH2 1.205 4'-COOH 2'-CeH5 2-CI 4-COOH 1.206 4'-COOH 2'~C6H5 2-CN 4-CONH2 1.207 4'-COOH 2'-CβH5 2-CH3 4-CSNH2 1.208 4'-COOH 2'-C6H5 2-CF3 4-NHCONH2 1.209 4'-COOH 2'-C6H5 2-OCF3 4-NHCSNH2 1.210 4'-COOH 2'-C6H5 2-SCF3 4-OCSNH2 1.211 4'-COOH H H 1.212 4'-COOH 4-F H 1.213 4'-COOH 4-CI H 1.214 4'-COOH 4-CN H 1.215 4'-COOH 4-CH3 H 1.216 4'-COOH 4-CF3 H 1.217 4'-COOH 4-OCF3 H 1.218 4'-COOH 4-SCF3 H 1.219 4'-COOH 4-S(0)CF3 H 1.220 4'-COOH 4-S(0)2CF3 H 1.221 4'-COOH 2-F H 1.222 4'-COOH 2-CI H 1.223 4'-COOH 2-CN H 1.224 4'-COOH 2-CH3 H 1.225 4'-COOH 2-CF3 H 1.226 4'-COOH 2-OCF3 H 1.227 4'-COOH 2-SCF3 H 1.228 4'-COOH 2-S(0)CF3 H 1.229 4'-COOH 2-S(0)2CF3 H 1.230 4'-COOH
Figure imgf000046_0001
H 4-NH2 1.231 4'-COOH 2'-(C6H4-4-CI) H 4-COOH
1.232 4'-COOH 2'-(C6H4-4-Cl) H 4-CONH2
1.233 4'-COOH 2'-(C6H4-4-CI) H 4-CSNH2
1.234 4'-COOH 2'-(C6H4-4-CI) H 4-NHCONH2
1.235 4'-COOH 2'-(C6H4-4-CI) H 4-NHCSNH2
1.236 4'-COOH 2'-(C6H4-4-CI) H 4-OCSNH2
1.237 4'-COOH 2'-(C6H4-4-CI) H 3-OC(F2)0-4
1.238 4'-COOH 2'-(C6H4-4-CI) H 3-SC(F2)S-4
1.239 4'-COOH 2'-(C6H4-4-CI) 2-F 4-NH2
1.240 4'-COOH 2'-(C6H4-4-CI) 2-CI 4-COOH
1.241 4'-COOH 2'-(C6H4-4-CI) 2-CN 4-CONH2
1.242 4'-COOH 2'-(C6H4-4-CI) 2-CH3 4-CSNH2
1.243 4'-COOH 2'-(C6H4-4-CI) 2-CF3 4-NHCONH2
1.244 4'-COOH 2'-(C6H4-4-Cl) 2-OCF3 4-NHCSNH2
1.245 4'-COOH 2'-(C6H4-4-CI) 2-SCF3 4-OCSNH2
1.246 4'-COOH 2'-(C6H3-2,4-CI2; H H
1.247 4'-COOH 2'-(C6H3-2,4-CI2] 4-F H
1.248 4'-COOH 2'-(C6H3-2,4-CI2 1 4-CI H
1.249 4'-COOH 2'-(C6H3-2,4-CI2 4-CN H
1.250 4'-COOH 2'-(C6H3-214-Cl2, 1 4-CH3 H
1.251 4'-COOH 2'-(C6H3-2,4-CI2 4-CF3 H
1.252 4'-COOH 2'-(C6H3-2,4-CI2 ) 4-OCF3 H
1.253 4'-COOH 2'-(C6H3-2,4-CI2 1 4-SCF3 H
1.254 4'-COOH 2'-(C6H3-2,4-CI2; 4-S(0)CF3 H
1.255 4'-COOH 2'-(C6H3-2,4-CI2, 4-S(0)2CF3 H
1.256 4'-COOH 2'-(C6H3-2,4-C)2; 2-F H
1.257 4'-COOH 2'-(C6H3-2,4-Cyι 2-CI H
1.258 4'-COOH 2'-(C6H3-2,4-Cl2; 1 2-CN H
1.259 4'-COOH 2'-(C6H3-2,4-CI2 2-CH3 H
1.260 4'-COOH 2'-(C6H3-2,4-CI2 1 2-CF3 H
1.261 4'-COOH 2'-(C6H3-2,4-CI2 2-OCF3 H
1.262 4'-COOH 2'-(C6H3-2,4-CI2 ) 2-SCFg H
1.263 4'-COOH 2'-(C6H3-2,4-CI2 ) 2-S(0)CF3 H
1.264 4'-COOH 2'-(C6H3-2,4-CI2 ) 2-S(0)2CF3 H 1.265 4'-COOH 2'-(C6H3-2,4-CI2) H 4-NH2
1.266 4'-COOH 2'-(C6H3-2,4-CI2) H 4-COOH
1.267 4'-COOH 2'-(C6H3-2,4-CI2) H 4-CONH2
1.268 4'-COOH 2'-(C6H3-2,4-CI2) H 4-CSNH2
1.269 4'-COOH 2'-(C6H3-2,4-CI2) H 4-NHCONH2
1.270 4'-COOH 2'-(C6H3-2,4-CI2) H 4-NHCSNH2
1.271 4'-COOH 2'-(C6H3-2,4-Cl2) H 4-OCSNH2
1.272 4'-COOH 2'-(C6H3-2,4-CI2) H 3-OC(F2)0-4
1.273 4'-COOH 2'-(C6H3-2,4-CI2) H 3-SC(F2)S-4
1.274 4'-COOH 2'-(C6H3-2,4-CI2) 2-F 4-NH2
1.275 4'-COOH 2'-(C6H3-2,4-CI2) 2-CI 4-COOH
1.276 4'-COOH 2'-(C6H3-2,4-CI2) 2-CN 4-CONH2
1.277 4'-COOH 2'-(C6H3-2,4-CI2) 2-CH3 4-CSNH2
1.278 4'-COOH 2'-(C6H3-2,4-CI2) 2-CF3 4-NHCONH2
1.279 4'-COOH 2'-(C6H3-2,4-CI2) 2-OCF3 4-NHCSNH2
1.280 4'-COOH 2'-(C6H3-2,4-CI2) 2-SCF3 4-OCSNH2
1.281 4'-CONH2 H H H
1.282 4'-CONH2 H 4-F H
1.283 4'-CONH2 H 4-CI H
1.284 4'-CONH2 H 4-CN H
1.285 4'-CONH2 H 4-CH3 H
1.286 4'-CONH2 H 4-CF3 H
1.287 4'-CONH2 H 4-OCF3 H
1.288 4'-CONH2 H 4-SCF3 H
1.289 4'-CONH2 H 4-S(0)CF3 H
1.290 4'-CONH2 H 4-S(0)2CF3 H
1.291 4'-CONH2 H 2-F H
1.292 4'-CONH2 H 2-CI H
1.293 4'-CONH2 H 2-CN H
1.294 4'-CONH2 H 2-CH3 H
1.295 4'-CONH2 H 2-CF3 H
1.296 4'-CONH2 H 2-OCF3 H
1.297 4'-CONH2 H 2-SCF3 H
1.298 4'-CONH2 H 2-S(0)CF3 H 1.299 4'-CONH2 H 2-S(0)2CF3 H
1.300 4'-CONH2 H H 4-NH2
1.301 4'-CONH2 H H 4-COOH
1.302 4'-CONH2 H H 4-CONH2
1.303 4'-CONH2 H H 4-CSNH2
1.304 4'-CONH2 H H 4-NHCONH2
1.305 4'-CONH2 H H 4-NHCSNH2
1.306 4'-CONH2 H H 4-OCSNH2
1.307 4'-CONH2 H H 3-OC(F2)0-4
1.308 4'-CONH2 H H 3-SC(F2)S-4
1.309 4'-CONH2 H 2-F 4-NH2
1.310 4'-CONH2 H 2-CI 4-COOH
1.311 4'-CONH2 H 2-CN 4-CONH2
1.312 4'-CONH2 H 2-CH3 4-CSNH2
1.313 4'-CONH2 H 2-CF3 4-NHCONH2
1.314 4'-CONH2 H 2-OCF3 4-NHCSNH2
1.315 4'-CONH2 H 2-SCF3 4-OCSNH2
1.316 4'-CONH2 2'-CN H H
1.317 4'-CONH2 2'-CN 4-F H
1.318 4'-CONH2 2'-CN 4-CI H
1.319 4'-CONH2 2'-CN 4-CN H
1.320 4'-CONH2 2'-CN 4-CH3 H
1.321 4'-CONH2 2'-CN 4-CF3 H
1.322 4'-CONH2 2'-CN 4-OCF3 H
1.323 4'-CONH2 2'-CN 4-SCF3 H
1.324 4'-CONH2 2'-CN 4-S(0)CF3 H
1.325 4'-CONH2 2'-CN 4-S(0)2CF3 H
1.326 4'-CONH2 2'-CN 2-F H
1.327 4'-CONH2 2'-CN 2-CI H
1.328 4'-CONH2 2'-CN 2-CN H
1.329 4'-CONH2 2'-CN 2-CH3 H
1.330 4'-CONH2 2'-CN 2-CF3 H
1.331 4'-CONH2 2'-CN 2-OCF3 H
1.332 4'-CONH2 2'-CN 2-SCF3 H 1.333 4'-CONH2 2'-CN 2-S(0)CF3 H
1.334 4'-CONH2 2'-CN 2-S(0)2CF3 H
1.335 4'-CONH2 2'-CN H 4-NH2
1.336 4'-CONH2 2'-CN H 4-COOH
1.337 4'-CONH2 2'-CN H 4-CONH2
1.338 4'-CONH2 2'-CN H 4-CSNH2
1.339 4'-CONH2 2'-CN H 4-NHCONH2
1.340 4'-CONH2 2'-CN H 4-NHCSNH2
1.341 4'-CONH2 2'-CN H 4-OCSNH2
1.342 4'-CONH2 2'-CN H 3-OC(F2)0-4
1.343 4'-CONH2 2'-CN H 3-SC(F2)S-4
1.344 4'-CONH2 2'-CN 2-F 4-NH2
1.345 4'-CONH2 2'-CN 2-CI 4-COOH
1.346 4'-CONH2 2'-CN 2-CN 4-CONH2
1.347 4'-CONH2 2'-CN 2-CH3 4-CSNH2
1.348 4'-CONH2 2'-CN 2-CF3 4-NHCONH2
1.349 4'-CONH2 2'-CN 2-OCF3 4-NHCSNH2
1.350 4'-CONH2 2'-CN 2-SCF3 4-OCSNH2
1.351 4'-CONH2 2'-CH3 H H
1.352 4'-CONH2 2'-CH3 4-F H
1.353 4'-CONH2 2'-CH3 4-CI H
1.354 4'-CONH2 2'-CH3 4-CN H
1.355 4'-CONH2 2'-CH3 4-CH3 H
1.356 4'-CONH2 2'-CH3 4-CF3 H
1.357 4'-CONH2 2'-CH3 4-0CF3 H
1.358 4'-CONH2 2'-CH3 4-SCF3 H
1.359 4'-CONH2 2'-CH3 4-S(0)CF3 H
1.360 4'-CONH2 2'-CH3 4-S(0)2CF3 H
1.361 4'-CONH2 2'-CH3 2-F H
1.362 4'-CONH2 2'-CH3 2-CI H
1.363 4'-CONH2 2'-CH3 2-CN H
1.364 4'-CONH2 2'-CH3 2-CH3 H
1.365 4'-CONH2 2'-CH3 2-CF3 H
1.366 4'-CONH2 2'-CH3 2-0CF3 H 1.367 4'-CONH2 2'-CH3 2-SCF3 H
1.368 4'-CONH2 2'-CH3 2-S(0)CF3 H
1.369 4'-CONH2 2'-CH3 2-S(0)2CF3 H
1.370 4'-CONH2 2'-CH3 H 4-NH2
1.371 4'-CONH2 2'-CH3 H 4-COOH
1.372 4'-CONH2 2'-CH3 H 4-CONH2
1.373 4'-CONH2 2'-CH3 H 4-CSNH2
1.374 4'-CONH2 2'-CH3 H 4-NHCONH2
1.375 4'-CONH2 2'-CH3 H 4-NHCSNH2
1.376 4'-CONH2 2'-CH3 H 4-OCSNH2
1.377 4'-CONH2 2'-CH3 H 3-OC(F2)0-4
1.378 4'-CONH2 2'-CH3 H 3-SC(F2)S-4
1.379 4'-CONH2 2'-CH3 2-F 4-NH2
1.380 4'-CONH2 2'-CH3 2-CI 4-COOH
1.381 4'-CONH2 2'-CH3 2-CN 4-CONH2
1.382 4'-CONH2 2'-CH3 2-CH3 4-CSNH2
1.383 4'-CONH2 2'-CH3 2-CF3 4-NHCONH2
1.384 4'-CONH2 2'-CH3 2-OCF3 4-NHCSNH2
1.385 4'-CONH2 2'-CH3 2-SCF3 4-OCSNH2
1.386 4'-CONH2 2'-CF3 H H
1.387 4'-CONH2 2'-CF3 4-F H
1.388 4'-CONH2 2'-CF3 4-CI H
1.389 4'-CONH2 2'-CF3 4-CN H
1.390 4'-CONH2 2'-CF3 4-CH3 H
1.391 4'-CONH2 2'-CF3 4-CF3 H
1.392 4'-CONH2 2'-CF3 4-OCF3 H m.p. 104-10°
1.393 4'-CONH2 2'-CF3 4-SCF3 H
1.394 4'-CONH2 2'-CF3 4-S(0)CF3 H
1.395 4'-CONH2 2'-CF3 4-S(0)2CF3 H
1.396 4'-CONH2 2'-CF3 2-F H
1.397 4'-CONH2 2'-CF3 2-CI H
1.398 4'-CONH2 2'-CF3 2-CN H
1.399 4'-CONH2 2'-CF3 2-CH3 H
1.400 4'-CONH2 2'-CF3 2-CF3 H 1.401 4'-CONH2 2'-CF3 2-OCF3 H
1.402 4'-CONH2 2'-CF3 2-SCF3 H
1.403 4'-CONH2 2'-CF3 2-S(0)CF3 H
1.404 4'-CONH2 2'-CF3 2-S(0)2CF3 H
1.405 4'-CONH2 2'-CF3 H 4-NH2
1.406 4'-CONH2 2'-CF3 H 4-COOH
1.407 4'-CONH2 2'-CF3 H 4-CONH2
1.408 4'-CONH2 2'-CF3 H 4-CSNH2
1.409 4'-CONH2 2'-CF3 H 4-NHCONH2
1.410 4'-CONH2 2'-CF3 H 4-NHCSNH2
1.411 4'-CONH2 2'-CF3 H 4-OCSNH2
1.412 4'-CONH2 2'-CF3 H 3-OC(F2)0-4
1.413 4'-CONH2 2'-CF3 H 3-SC(F2)S-4
1.414 4'-CONH2 2'-CF3 2-F 4-NH2
1.415 4'-CONH2 2'-CF3 2-CI 4-COOH
1.416 4'-CONH2 2'-CF3 2-CN 4-CONH2
1.417 4'-CONH2 2'-CF3 2-CH3 4-CSNH2
1.418 4'-CONH2 2'-CF3 2-CF3 4-NHCONH2
1.419 4'-CONH2 2'-CF3 2-OCF3 4-NHCSNH2
1.420 4'-CONH2 2'-CF3 2-SCF3 4-OCSNH2
1.421 4'-CONH2 2'-OCF3 H H
1.422 4'-CONH2 2'-OCF3 4-F H
1.423 4'-CONH2 2'-OCF3 4-CI H
1.424 4'-CONH2 2'-OCF3 4-CN H
1.425 4'-CONH2 2'-OCF3 4-CH3 H
1.426 4'-CONH2 2'-OCF3 4-CF3 H
1.427 4'-CONH2 2'-OCF3 4-OCF3 H
1.428 4'-CONH2 2'-OCF3 4-SCF3 H
1.429 4'-CONH2 2'-OCF3 4-S(0)CF3 H
1.430 4'-CONH2 2'-OCF3 4-S(0)2CF3 H
1.431 4'-CONH2 2'-OCF3 2-F H
1.432 4'-CONH2 2'-OCF3 2-CI H
1.433 4'-CONH2 2'-OCF3 2-CN H
1.434 4'-CONH2 2'-OCF3 2-CH3 H 1.435 4'-C0NH2 2'-OCF3 2-CF3 H
1.436 4'-C0NH2 2'-OCF3 2-OCF3 H
1.437 4'-CONH2 2'-OCF3 2-SCF3 H
1.438 4'-CONH2 2'-OCF3 2-S(0)CF3 H
1.439 4'-CONH2 2'-OCF3 2-S(0)2CF3 H
1.440 4'-CONH2 2'-OCF3 H 4-NH2
1.441 4'-CONH2 2'-OCF3 H 4-COOH
1.442 4'-CONH2 2'-OCF3 H 4-CONH2
1.443 4'-CONH2 2'-OCF3 H 4-CSNH2
1.444 4'-CONH2 2'-OCF3 H 4-NHCONH2
1.445 4'-CONH2 2'-OCF3 H 4-NHCSNH2
1.446 4'-CONH2 2'-OCF3 H 4-OCSNH2
1.447 4'-CONH2 2'-OCF3 H 3-OC(F2)0-4
1.448 4'-CONH2 2'-OCF3 H 3-SC(F2)S-4
1.449 4'-CONH2 2'-OCF3 2-F 4-NH2
1.450 4'-CONH2 2'-OCF3 2-CI 4-COOH
1.451 4'-CONH2 2'-OCF3 2-CN 4-CONH2
1.452 4'-CONH2 2'-OCF3 2-CH3 4-CSNH2
1.453 4'-CONH2 2'-OCF3 2-CF3 4-NHCONH2
1.454 4'-CONH2 2'-OCF3 2-OCF3 4-NHCSNH2
1.455 4'-CONH2 2'-OCF3 2-SCF3 4-OCSNH2
1.456 4'-CONH2 2'-C6H5 H H
1.457 4'-CONH2 2'-CeH5 4-F H
1.458 4'-CONH2 2'-CeH5 4-CI H
1.459 4'-CONH2 2'-CeH5 4-CN H
1.460 4'-CONH2 2'-C6H5 4-CH3 H
1.461 4'-CONH2 2'-CeH5 4-CF3 H
1.462 4'-CONH2 2'-CeH5 4-OCF3 H
1.463 4'-CONH2 2'-C6H5 4-SCF3 H
1.464 4'-CONH2 2'-C6H5 4-S(0)CF3 H
1.465 4'-CONH2 2'-C6H5 4-S(0)2CF3 H
1.466 4'-CONH2 2'-C6H5 2-F H
1.467 4'-CONH2 2'-C6H5 2-CI H
1.468 4'-CONH2 2'-C6H5 2-CN H 1.469 4'-CONH2 2'-C6H5 2-CH3 H
1.470 4'-CONH2 2'-C6H5 2-CF3 H
1.471 4'-CONH2 2'-C6H5 2-OCF3 H
1.472 4'-CONH2 2'-C6H5 2-SCF3 H
1.473 4'-CONH2 2'-C6H5 2-S(0)CF3 H
1.474 4'-CONH2 2'-C6H5 2-S(0)2CF3 H
1.475 4'-CONH2 2'-C6H5 H 4-NH2
1.476 4'-CONH2 2'-CsH5 H 4-COOH
1.477 4'-CONH2 2'-C6H5 H 4-CONH2
1.478 4'-CONH2 2'-C6H5 H 4-CSNH2
1 .479 4'-CONH2 2'-C6H5 H 4-NHCONH2
1 .480 4'-CONH2 '-C6H5 H 4-NHCSNH2
1.481 4'-CONH2 2'-C6H5 H 4-OCSNH2
1.482 4'-CONH2 2'-C6H5 H 3-OC(F2)0-4
1.483 4'-CONH2 2'-C6H5 H 3-SC(F2)S-4
1.484 4'-CONH2 2'-C6H5 2-F 4-NH2
1.485 4'-CONH2 2'-C6H5 2-CI 4-COOH
1.486 4'-CONH2 2'-C6H5 2-CN 4-CONH2
1.487 4'-CONH2 2'-C6H5 2-CH3 4-CSNH2
1.488 4'-CONH2 2'-C6H5 2-CF3 4-NHCONH2
1.489 4'-CONH2 2'-CsH5 2-OCF3 4-NHCSNH2
1.490 4'-CONH2 2'-C6H5 2-SCF3 4-OCSNH2
1.491 4'-CONH2 2'-(C6H4 -4-CI) H H
1.492 4'-CONH2 2'-(C6H4 -4-CI) 4-F H
1.493 4'-CONH2 2'-(C6H4 -4-Cl) 4-CI H
1.494 4'-CONH2 2'-(C6H4 -4-CI) 4-CN H
1.495 4'-CONH2 2'-(C8H4 -4-CI) 4-CH3 H
1.496 4'-CONH2 2'-(C6H4 -4-CI) 4-CF3 H
1 .497 4'-CONH2 2'-(C6H4 -4-CI) 4-OCF3 H
1.498 4'-CONH2 2'-(CeH4 -4-CI) 4-SCF3 H
1.499 4'-CONH2 2'-(C6H4 -4-CI) 4-S(0)CF3 H
1.500 4'-CONH2 2'-(C8H4 -4-CI) 4-S(0)2CF3 H
1.501 4'-CONH2 2'-(C6H4 -4-CI) 2-F H
1.502 4'-CONH2 2'-(CeH -4-CI) 2-CI H 1.503 4'-CONH2 2'-(C6H4-4-CI) 2-CN H
1.504 4'-CONH2 2'-(C6H4-4-CI) 2-CH3 H
1.505 4'-CONH2 2'-(C6H4-4-CI) 2-CF3 H
1.506 4'-CONH2 2'-(C6H4-4~CI) 2-OCF3 H
1.507 4'-CONH2 2'-(C6H4-4-CI) 2-SCF3 H
1.508 4'-CONH2 2'-(C6H4-4-CI) 2-S(0)CF3 H
1.509 4'-CONH2 2'-(C6H4-4-C!) 2-S(0)2CF3 H
1.510 4'-CONH2 2'-(C6H4-4-CI) H 4-NH2
1.511 4'-CONH2 2'-(C6H4-4-CI) H 4-COOH
1.512 4'-CONH2 2'-(C6H4-4-Cl) H 4-CONH2
1.513 4'-CONH2 2'-(C6H4-4-CI) H 4-CSNH2
1.514 4'-CONH2 2'-(C6H4-4-CI) H 4-NHCONH2
1.515 4'-CONH2 2'-(C6H4-4-CI) H 4-NHCSNH2
1.516 4'-CONH2 2'-(C6H4-4-CI) H 4-OCSNH2
1.517 4'-CONH2 2'-(C6H4-4-CI) H 3-OC(F2)0-4
1.518 4'-CONH2 2'-(C6H4-4-CI) H 3-SC(F2)S-4
1.519 4'-CONH2 2'-(C6H4-4-CI) 2-F 4-NH2
1.520 4'-CONH2 2'-(C6H4-4-CI) 2-CI 4-COOH
1.521 4'-CONH2 2'-(C6H4-4-CI) 2-CN 4-CONH2
1.522 4'-CONH2 2'-(C6H4-4-CI) 2-CH3 4-CSNH2
1.523 4'-CONH2 2'-(C6H4-4-CI) 2-CF3 4-NHCONH2
1.524 4'-CONH2 2'-(C6H4-4-CI) 2-0CF3 4-NHCSNH2
1.525 4'-CONH2 2'-(C6H4-4-CI) 2-SCF3 4-OCSNH2
1.526 4'-CONH2 2'-(C6H3-2,4-CI2) H H
1.527 4'-CONH2 2'-(C6H3-2,4-Cl2) 4-F H
1.528 4'-CONH2 2'-(C6H3-2,4-CI2) 4-CI H
1.529 4'-CONH2 2'-(C6H3-2,4-CI2) 4-CN H
1.530 4'-CONH2 2'-(C6H3-2,4-CI2) 4-CH3 H
1.531 4'-CONH2 2'-(C6H3-2,4-CI2) 4-CF3 H
1.532 4'-CONH2 2'-(C6H3-2,4-CI2) 4-OCF3 H
1.533 4'-CONH2 2'-(C6H3-2,4-CI2) 4-SCF3 H
1.534 4'-CONH2 2'-(C6H3-2,4-CI2) 4-S(0)CF3 H
1.535 4'-CONH2 2'-(C6H3-2,4-CI2) 4-S(0)2CF3 H
1.536 4'-CONH2 2'-(C6H3-2,4-CI2) 2-F H 1.537 4'-CONH2 2'-(C6H3-2,4-CI2] 2-CI H
1.538 4'-CONH2 2*-(CβH3-2,4-CV 2-CN H
1.539 4'-CONH2 2'-(C6H3-2,4-CI2; 2-CH3 H
1.540 4'-CONH2 2'-(C6H3-2,4-CI2] 2-CF3 H
1.541 4'-CONH2 2'-(C6H3-2!4-CI2 , 2-OCF3 H
1.542 4'-CONH2 2'-(C6H3-2,4-CI2; 2-SCF3 H
1.543 4'-CONH2 2'-(C6H3-2,4-Cyι I 2-S(0)CF3 H
1.544 4'-CONH2 2'-(C6H3-2,4-CI2; ) 2-S(0)2CF3 H
1.545 4'-CONH2 2'-(C6H3-2,4-CI2; I H 4-NH2
1.546 4'-CONH2 2'-(C6H3-2,4-CI2 H 4-COOH
1.547 4'-CONH2 ^(dH^-CI,1 ) H 4-CONH2
1.548 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 4-CSNH2
1.549 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 4-NHCONH2
1.550 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 4-NHCSNH2
1.551 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 4-OCSNH2
1.552 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 3-OC(F2)0-4
1.553 4'-CONH2 2'-(C6H3-2,4-CI2 ) H 3-SC(F2)S-4
1.554 4'-CONH2 2'-(C6H3-2,4-CI2 I 2-F 4-NH2
1.555 4'-CONH2 2'-(C6H3-2,4-CI2 I 2-CI 4-COOH
1.556 4'-CONH2 2'-(C6H3-2,4-CI2 > 2-CN 4-CONH2
1.557 4'-CONH2 2'-(C6H3-2,4-CI2; I 2-CH3 4-CSNH2
1.558 4'-CONH2 2'-(C6H3-2,4-CI2 ) 2-CF3 4-NHCONH2
1.559 4'-CONH2 ^-(CeH^^-CI^ | 2-0CF3 4-NHCSNH2
1.560 4'-CONH2 2'-(C6H3-2,4-CI2 ) 2-SCF3 4-OCSNH2
1.561 4'-CONH2 2'-OC6H5 H H
1.562 4'-CONH2 2'-OC6H5 4-F H
1.563 4'-CONH2 2'-OC6H5 4-CI H
1.564 4'-CONH2 2'-OC6H5 4-CN H
1.565 4'-CONH2 2'-OC6H5 4-CH3 H
1.566 4'-CONH2 2'-OC6H5 4-CF3 H
1.567 4'-CONH2 2'-OC6H5 4-OCF3 H
1.568 4'-CONH2 2'-OC6H5 4-SCF3 H
1.569 4'-CONH2 2'-OC6H5 4-S(0)CF3 H
1.570 4'-CONH2 2'-OC6H5 4-S(0)2CF3 H 1.571 4'-CONH2 2'-OC6H5 2-F H
1.572 4'-CONH2 2'-OC6H5 2-CI H
1.573 4'-CONH2 2'-OC6H5 2-CN H
1.574 4'-CONH2 2'-OC6H5 2-CH3 H
1.575 4'-CONH2 2'-OC6H5 2-CF3 H
1.576 4'-CONH2 2'-OC6H5 2-OCF3 H
1.577 4'-CONH2 2'-OC6H5 2-SCF3 H
1.578 4'-CONH2 2'-OC6H5 2-S(0)CF3 H
1.579 4'-CONH2 2'-OC6H5 2-S(0)2CF3 H
1.580 4'-CONH2 2'-OC6H5 H 4-NH2
1.581 4'-CONH2 2'-OC6H5 H 4-COOH
1.582 4'-CONH2 2'-OC6H5 H 4-CONH2
1.583 4'-CONH2 2'-OC6H5 H 4-CSNH2
1.584 4'-CONH2 2'-OC6H5 H 4-NHCONH2
1.585 4'-CONH2 2'-OC6H5 H 4-NHCSNH2
1.586 4'-CONH2 2'-OC6H5 H 4-OCSNH2
1.587 4'-CONH2 2'-OC6H5 H 3~OC(F2)0-4
1.588 4'-CONH2 2'-OC6H5 H 3-SC(F2)S-4
1.589 4'-CONH2 2'-OC6H5 2-F 4-NH2
1.590 4'-CONH2 2'-OC6H5 2-CI 4-COOH
1.591 4'-CONH2 2'-OC6H5 2-CN 4-CONH2
1.592 4'-CONH2 2'-OC6Hs 2-CH3 4-CSNH2
1.593 4'-CONH2 2'-OC6H5 2-CF3 4-NHCONH2
1.594 4'-CONH2 2'-OC6H5 2-OCF3 4-NHCSNH2
1.595 4'-CONH2 2'-OC6H5 2-SCF3 4-OCSNH2
1.596 4'-CONH2 2'-(OC6H4- ■4-CI) H H
1.597 4'-CONH2 2'-(OC6H4 -4-CI) 4-F H
1.598 4'-CONH2 2'-(OC6H4 -4-CI) 4-CI H
1.599 4'-CONH2 2'-(OC6H4 -4-CI) 4-CN H
1.600 4'-CONH2 2'-(OC6H4 -4-CI) 4-CH3 H
1.601 4'-CONH2 2'-(OC6H4 -4-CI) 4-CF3 H
1.602 4'-CONH2 2'-(OC6H4 -4-CI) 4-OCF3 H
1.603 4'-CONH2 2'-(OC6H4 -4-CI) 4-SCF3 H
1.604 4'-CONH2 2'-(OC6H4 -4-CI) 4-S(0)CF3 H 1.605 4'-CONH2 2'-(OC6H4-4-CI) 4-S(0)2CF3 H
1.606 4'-CONH2 2'-(OC6H4-4-CI) 2-F H
1.607 4'-CONH2 2'-(OC6H4-4-CI) 2-CI H
1.608 4'-CONH2 2'-(OC6H4-4-CI) 2-CN H
1.609 4'-CONH2 2'-(OC6H4-4-CI) 2-CH3 H
1.610 4'-CONH2 2'-(OC6H4-4-CI) 2-CF3 H
1.611 4'-CONH2 2'-(OC6H4-4-Cl) 2-OCF3 H
1.612 4'-CONH2 2'-(OC6H4-4-CI) 2-SCF3 H
1.613 4'-CONH2 2'-(OC6H4-4-CI) 2-S(0)CF3 H
1.614 4'-CONH2 2'-(OC6H4-4-CI) 2-S(0)2CF3 H
1.615 4'-CONH2 2'-(OC6H4-4-CI) H 4-NH2
1.616 4'-CONH2 2'-(OC6H4-4-CI) H 4-COOH
1.617 4'-CONH2 2'-(OC6H4-4-CI) H 4-CONH2
1.618 4'-CONH2 2'-(OC6H4-4-CI) H 4-CSNH2
1.619 4'-CONH2 2'-(OC6H4-4-CI) H 4-NHCONH2
1.620 4'-CONH2 2'-(OC6H4-4-CI) H 4-NHCSNH2
1.621 4'-CONH2 2'-(OC6H4-4-CI) H 4-OCSNH2
1.622 4'-CONH2 2'-(OC6H4-4-CI) H 3-OC(F2)0-4
1.623 4'-CONH2 2'-(OC6H4-4-CI) H 3-SC(F2)S-4
1.624 4'-CONH2 2'-(OC6H4-4-Cl) 2-F 4-NH2
1.625 4'-CONH2 2'-(OC6H4-4-CI) 2-CI 4-COOH
1.626 4'-CONH2 2'-(OC6H4-4-CI) 2-CN 4-CONH2
1.627 4'-CONH2 2'-(OC6H4-4-CI) 2-CH3 4-CSNH2
1.628 4'-CONH2 2'-(OC6H4-4-CI) 2-CF3 4-NHCONH2
1.629 4'-CONH2 2'-(OC6H4-4-CI) 2-OCF3 4-NHCSNH2
1.630 4'-CONH2 2'-(OC6H4-4-CI) 2-SCF3 4-OCSNH2
1.631 4'-CONH2 2'-(OC6H3-2,4-CI2) H H
1.632 4'-CONH2 2'-(OC6H3-2,4-Cl2) 4-F H
1.633 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-CI H
1.634 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-CN H
1.635 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-CH3 H
1.636 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-CF3 H
1.637 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-OCF3 H
1.638 4'-CONH2 2'-(OC6H3-2,4-CI2) 4-SCF3 H 1.639 4'-CONH2 2'-(OC6H3-2,4-Cl2) 4-S(0)CF3 H
1.640 4'-CONH2 2'-(OC6H3-2,4-Cl2) 4-S(0)2CF3 H
1.641 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-F H
1.642 4'-CONH2 2'-(OC6H3-2,4-Cl2) 2-CI H
1.643 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-CN H
1.644 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-CH3 H
1.645 4'-CONH2 2'-(OC6H3-2,4-Cl2) 2-CF3 H
1.646 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-OCF3 H
1.647 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-SCF3 H
1.648 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-S(0)CF3 H
1.649 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-S(0)2CF3 H
1.650 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-NH2
1.651 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-COOH
1.652 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-CONH2
1.653 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-CSNH2
1.654 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-NHCONH2
1.655 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-NHCSNH2
1.656 4'-CONH2 2'-(OC6H3-2,4-CI2) H 4-OCSNH2
1.657 4'-CONH2 2'-(OC6H3-2,4-CI2) H 3-OC(F2)0-4
1.658 4!-CONH2 2'-(OC6H3-2,4-CI2) H 3-SC(F2)S-4
1.659 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-F 4-NH2
1.660 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-CI 4-COOH
1.661 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-CN 4-CONH2
1.662 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-CH3 4-CSNH2
1.663 4'-CONH2 2'-(OC6H3-2,4-Cl2) 2-CF3 4-NHCONH2
1.664 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-OCF3 4-NHCSNH2
1.665 4'-CONH2 2'-(OC6H3-2,4-CI2) 2-SCFg 4-OCSNH2
1.666 5'-COOH H H H
1.667 5'-COOH H 4-F H
1.668 5'-COOH H 4-CI H
1.669 5'-COOH H 4-CN H
1.670 5'-COOH H 4-CH3 H
1.671 5'-COOH H 4-CF3 H
1.672 5'-COOH H 4-OCF3 H 1.673 5'-COOH H 4-SCF3 H
1.674 5'-COOH H 4-S(0)CF3 H
1.675 5'-COOH H 4-S(0)2CF3 H
1.676 5'-COOH H 2-F H
1.677 5'-COOH H 2-CI H
1.678 5'-COOH H 2-CN H
1.679 5'-COOH H 2-CH3 H
1.680 5'-COOH H 2-CF3 H
1.681 S'-COOH H 2-OCF3 H
1.682 5'-COOH H 2-SCF3 H
1.683 5'-COOH H 2-S(0)CF3 H
1.684 5'-COOH H 2-S(0)2CF3 H
1.685 5'-COOH H H 4-NH2
1.686 5'-COOH H H 4-COOH
1.687 5'-COOH H H 4-CONH2
1.688 5'-COOH H H 4-CSNH2
1.689 5'-COOH H H 4-NHCONH2
1.690 5'-COOH H H 4-NHCSNH2
1.691 5'-COOH H H 4-OCSNH2
1.692 5'-COOH H H 3-OC(F2)0-4
1.693 5'-COOH H H 3-SC(F2)S-4
1.694 5'-COOH H 2-F 4-NH2
1.695 5'-COOH H 2-CI 4-COOH
1.696 5'-COOH H 2-CN 4-CONH2
1.697 5'-COOH H 2-CH3 4-CSNH2
1.698 5'-COOH H 2-CF3 4-NHCONH2
1.699 5'-COOH H 2-OCF3 4-NHCSNH2
1.700 5'-COOH H 2-SCF3 4-OCSNH2
1.701 5'-COOH 2'- CN H H
1.702 5'-COOH 2'- CN 4-F H
1.703 5'-COOH 2'- CN 4-CI H
1.704 5'-COOH 2'- CN 4-CN H
1.705 5'-COOH 2'- CN 4-CH3 H
1.706 5'-COOH 2'- CH 4-CF3 H 1.707 5'-COOH 2'-CN 4-OCF3 H
1.708 5'-COOH 2'-CN 4-SCF3 H
1.709 5'-COOH 2'-CN 4-S(0)CF3 ■ H
1.710 5'-COOH 2'-CN 4-S(0)2CF3 H
1.711 5'-COOH 2'-CN 2-F H
1.712 5'-COOH 2'-CN 2-CI H
1.713 5'-COOH 2'-CN 2-CN H
1.714 5'-COOH 2'-CN 2-CH3 H
1.715 5'-COOH 2'-CN 2-CF3 H
1.716 5'-COOH 2'-CN 2-OCF3 H
1.717 5'-COOH 2'-CN 2-SCF3 H
1.718 5'-COOH 2'-CN 2-S(0)CF3 H
1.719 5'-COOH 2'-CN 2-S(0)2CF3 H
1.720 5'-COOH 2'-CN H 4-NH2
1.721 5'-COOH 2'-CN H 4-COOH
1.722 5'-COOH 2'-CN H 4-CONH2
1.723 δ'-COOH 2'-CN H 4-CSNH2
1.724 5'-COOH 2'-CN H 4-NHCONH2
1.725 5'-COOH 2'-CN H 4-NHCSNH2
1.726 5'-COOH 2'-CN H 4-OCSNH2
1.727 5'-COOH 2'-CN H 3-OC(F2)0-4
1.728 5'-COOH 2'-CN H 3-SC(F2)S-4
1.729 5'-COOH 2'-CN 2-F 4-NH2
1.730 5'-COOH 2'-CN 2-CI 4-COOH
1.731 5'-COOH 2'-CN 2-CN 4-CONH2
1.732 5'-COOH 2'-CN 2-CH3 4-CSNH2
1.733 5'-COOH 2'-CN 2-CF3 4-NHCONH2
1.734 5'-COOH 2'-CN 2-OCF3 4-NHCSNH2
1.735 5'-COOH 2'-CN 2-SCF3 4-OCSNH2
1.736 5'-COOH 2'-CH3 H H
1.737 δ'-COOH 2'-CH3 4-F H
1.738 5'-COOH 2'-CH3 4-CI H
1.739 5'-COOH 2'-CH3 4-CN H
1.740 5'-COOH 2'-CH3 4-CH3 H 1.741 5'-COOH 2'-CH3 4-CF3 H
1.742 5!-COOH 2'-CH3 4-OCF3 H
1.743 5'-COOH 2'-CH3 4-SCF3 H
1.744 5'-COOH 2'-CH3 4-S(0)CF3 H
1.745 5'-COOH 2'-CH3 4-S(0)2CF3 H
1.746 5'-COOH 2'-CH3 2-F H
1.747 5'-COOH 2'-CH3 2-CI H
1.748 5'-COOH 2'-CH3 2-CN H
1.749 5'-COOH 2'-CH3 2-CH3 H
1.750 δ'-COOH 2'-CH3 2-CF3 H
1.751 5'-COOH 2'-CH3 2-OCF3 H
1.752 δ'-COOH 2'-CH3 2-SCF3 H
1.753 δ'-COOH 2'-CH3 2-S(0)CF3 H
1.754 δ'-COOH 2'-CH3 2-S(0)2CF3 H
1.755 δ'-COOH 2'-CH3 H 4-NH2
1.756 δ'-COOH 2'-CH3 H 4-COOH
1.757 δ'-COOH 2'-CH3 H 4-CONH2
1.758 δ'-COOH 2'-CH3 H 4-CSNH2
1.759 5'-COOH 2'-CH3 H 4-NHCONH2
1.760 5'-COOH 2'-CH3 H 4-NHCSNH2
1.761 δ'-COOH 2'-CH3 H 4-OCSNH2
1.762 δ'-COOH 2'-CH3 H 3-OC(F2)0-4
1.763 δ'-COOH 2'-CH3 H 3-SC(F2)S-4
1.764 δ'-COOH 2'-CH3 2-F 4-NH2
1.765 δ'-COOH 2'-CH3 2-CI 4-COOH
1.766 δ'-COOH 2'-CH3 2-CN 4-CONH2
1.767 δ'-COOH 2'-CH3 2-CHs 4-CSNH2
1.768 δ'-COOH 2'-CH3 2-CF3 4-NHCONH2
1.769 δ'-COOH 2'-CH3 2-OCF3 4-NHCSNH2
1.770 δ'-COOH 2'-CH3 2-SCF3 4-OCSNH2
1.771 δ'-COOH 2'-CF3 H H
1.772 5'-COOH 2'-CF3 4-F H
1.773 5'-COOH 2'-CF3 4-CI H
1.774 δ'-COOH 2'-CF3 4-CN H 1.775 5'-COOH 2'-CF3 4-CH3 H
1.776 δ'-COOH 2'-CF3 4-CF3 H
1.777 δ'-COOH 2'-CF3 4-OCF3 H m.p. 211-5°
1.778 δ'-COOH 2'-CF3 4-SCF3 H
1.779 δ'-COOH 2'-CF3 4-S(0)CF3 H
1.780 δ'-COOH 2'-CF3 4-S(0)2CF3 H
1.781 5'-COOH 2'-CF3 2-F H
1.782 δ'-COOH 2'-CF3 2-CI H
1.783 δ'-COOH 2'-CF3 2-CN H
1.784 δ'-COOH 2'-CF3 2-CH3 H
1.785 δ'-COOH 2'-CF3 2-CF3 H
1.786 δ'-COOH 2'-CF3 2-OCF3 H
1.787 δ'-COOH 2'-CF3 2-SCF3 H
1.788 δ'-COOH 2'-CF3 2-S(0)CF3 H
1.789 δ'-COOH 2'-CF3 2-S(0)2CF3 H
1.790 δ'-COOH 2'-CF3 H 4-NH2
1.791 δ'-COOH 2'-CF3 H 4-COOH
1.792 δ'-COOH 2'-CF3 H 4-CONH2
1.793 δ'-COOH 2'-CF3 H 4-CSNH2
1.794 δ'-COOH 2'-CF3 H 4-NHCONH2
1.795 5'-COOH 2'-CF3 H 4-NHCSNH2
1.796 5'-COOH 2'-CF3 H 4-OCSNH2
1.797 δ'-COOH 2'-CF3 H 3-OC(F2)0-4
1.798 5'-COOH 2'-CF3 H 3-SC(F2)S-4
1.799 δ'-COOH 2'-CF3 2-F 4-NH2
1.800 δ'-COOH 2'-CF3 2-CI 4-COOH
1.801 δ'-COOH 2'-CF3 2-CN 4-CONH2
1.802 δ'-COOH 2'-CF3 2-CH3 4-CSNH2
1.803 δ'-COOH 2'-CF3 2-CF3 4-NHCONH2
1.804 δ'-COOH 2'-CF3 2-0CF3 4-NHCSNH2
1.805 δ'-COOH 2'-CF3 2-SCF3 4-OCSNH2
1.806 5'-COOH 2'-OCF3 H H
1.807 5'-COOH 2'-OCF3 4-F H
1.808 δ'-COOH 2'-OCF3 4-CI H 1.809 5'-COOH 2'-OCF3 4-CN H
1.810 5'-COOH 2'-OCF3 4-CH3 H
1.811 δ'-COOH 2'-OCF3 4-CF3 H
1.812 δ'-COOH 2'-OCF3 4-OCF3 H
1.813 δ'-COOH 2'-OCF3 4-SCF3 H
1.814 δ'-COOH 2'-OCF3 4-S(0)CF3 H
1.815 5'-COOH 2'-OCF3 4-S(0)2CF3 H
1.816 5'-COOH 2'-OCF3 2-F H
1.817 5'-COOH 2'-OCF3 2-CI H
1.818 5'-COOH 2'-OCF3 2-CN H
1.819 5'-COOH 2'-OCF3 2-CH3 H
1.820 δ'-COOH 2'-OCF3 2-CF3 H
1.821 5'-COOH 2'-OCF3 2-OCF3 H
1.822 5'-COOH 2'-OCF3 2-SCF3 H
1.823 δ'-COOH 2'-OCF3 2-S(0)CF3 H
1.824 δ'-COOH 2'-OCF3 2-S(0)2CF3 H
1.825 δ'-COOH 2'-OCF3 H 4-NH2
1.826 δ'-COOH 2'-OCF3 H 4-COOH
1.827 5'-COOH 2'-OCF3 H 4-CONH2
1.828 5'-COOH 2'-OCF3 H 4-CSNH2
1.829 5'-COOH 2'-OCF3 H 4-NHCONH2
1.830 δ'-COOH 2'-OCF3 H 4-NHCSNH2
1.831 δ'-COOH 2'-OCF3 H 4-OCSNH2
1.832 δ'-COOH 2'-OCF3 H 3-OC(F2)0-4
1.833 δ'-COOH 2'-OCF3 H 3-SC(F2)S-4
1.834 δ'-COOH 2'-OCF3 2-F 4-NH2
1.835 5'-COOH 2'-OCF3 2-CI 4-COOH
1.836 δ'-COOH 2'-OCF3 2-CN 4-CONH2
1.837 5'-COOH 2'-OCF3 2-CH3 4-CSNH2
1.838 5'-COOH 2'-OCF3 2-CF3 4-NHCONH2
1.839 5'-COOH 2'-OCF3 2-OCF3 4-NHCSNH2
1.840 5'-COOH 2'-OCF3 2-SCF3 4-OCSNH2
1.841 5'-COOH 2'-C6H5 H H
1.842 5'-COOH 2'-C6H5 4-F H 1.843 5'-COOH 2'-C6H5 4-CI H
1.844 5'-COOH 2'-C6H5 4-CN H
1.845 5'-COOH 2'-C8H5 4-CH3 H
1.846 5'-COOH 2'-C6H5 4-CF3 H
1.847 5'-COOH 2'-C6H5 4-OCF3 H
1.848 5'-COOH 2'-C6H5 4-SCF3 H
1.849 5'-COOH 2'-C6H5 4-S(0)CF3 H
1.850 5'-COOH 2'-C6H5 4-S(0)2CF3 H
1.851 5'-COOH 2'-C6H5 2-F H
1.852 5'-COOH 2'-C6H5 2-CI H
1.853 δ'-COOH 2'-C6H5 2-CN H
1.854 δ'-COOH 2'-C6H5 2-CH3 H
1.855 δ'-COOH 2'-C8H5 2-CF3 H
1.856 5'-COOH 2'-C6H5 2-OCF3 H
1.857 5'-COOH 2'-C6H5 2-SCF3 H
1.858 5'-COOH 2'-C6H5 2-S(0)CF3 H
1.859 5'-COOH 2'-C6H5 2-S(0)2CF3 H
1.860 5'-COOH 2'-C6H5 H 4-NH2
1.861 5'-COOH 2'-C6H5 H 4-COOH
1.862 5'-COOH 2'-C6H5 H 4-CONH2
1.863 5'-COOH 2'-C6H5 H 4-CSNH2
1.864 5'-COOH 2'-C6H5 H 4-NHCONH2
1.865 δ'-COOH 2'-C6H5 H 4-NHCSNH2
1.866 δ'-COOH 2'-C6H5 H 4-OCSNH2
1.867 5'-COOH 2'-C6H5 H 3-OC(F2)0-4
1.868 5'-COOH 2'-C6H5 H 3-SC(F2)S-4
1.869 δ'-COOH 2'-C6H5 2-F 4-NH2
1.870 5'-COOH 2'-C6H5 2-C! 4-COOH
1.871 δ'-COOH 2'-CeH5 2-CN 4-CONH2
1.872 5'-COOH 2'-C6H5 2-CH3 4-CSNH2
1.873 5'-COOH 2'-C6H5 2-CF3 4-NHCONH2
1.874 5'-COOH 2'-C6H5 2-OCF3 4-NHCSNH2
1.875 δ'-COOH 2'-C6H5 2-SCF3 4-OCSNH2
1.876 5'-COOH 2'-(C6H4-4-CI) H H 1.877 5'-COOH 2'-(C6H4-4-CI) 4-F H
1.878 δ'-COOH 2'-(C6H4-4-CI) 4-CI H
1.879 δ'-COOH 2'-(C6H4-4-CI) 4-CN H
1.880 δ'-COOH 2'-(C6H4-4-CI) 4-CH3 H
1.881 δ'-COOH 2'-(C6H4-4-CI) 4-CF3 H
1.882 5'-COOH 2'-(C6H4-4-CI) 4-OCF3 H
1.883 5'-COOH 2'-(C6H4-4-CI) 4-SCF3 H
1.884 δ'-COOH 2'-(C6H4-4-CI) 4-S(0)CF3 H
1.885 δ'-COOH 2'-(C6H4-4-CI) 4-S(0)2CF3 H
1.886 δ'-COOH 2'-(C6H4-4-CI) 2-F H
1.887 δ'-COOH 2'-(C6H4-4-CI) 2-CI H
1.888 δ'-COOH 2'-(C6H4-4-CI) 2-CN H
1.889 δ'-COOH 2'-(C6H4-4-CI) 2-CH3 H
1.890 δ'-COOH 2'-(C6H4-4-Cl) 2-CF3 H
1.891 δ'-COOH 2'-(C6H4-4-CI) 2-OCF3 H
1.892 δ'-COOH 2'-(C6H4-4-CI) 2-SCF3 H
1.893 δ'-COOH 2'-(C6H4-4-CI) 2-S(0)CF3 H
1.894 5'-COOH 2'-(C6H4-4-CI) 2-S(0)2CF3 H
1.895 δ'-COOH 2'-(C6H4-4-CI) H 4-NH2
1.896 5'-COOH 2'-(C6H4-4-CI) H 4-COOH
1.897 5'-COOH 2'-(C6H4-4-CI) H 4-CONH2
1.898 5'-COOH 2'-(C6H4-4-CI) H 4-CSNH2
1.899 5'-COOH 2'-(C6H4-4-CI) H 4-NHCONH2
1.900 δ'-COOH 2'-(C6H4-4-CI) H 4-NHCSNH2
1.901 5'-COOH 2'-(C6H4-4-CI) H 4-OCSNH2
1.902 5'-COOH 2'-(C6H4-4-CI) H 3-OC(F2)0-4
1.903 δ'-COOH 2'-(C6H4-4-Cl) H 3-SC(F2)S-4
1.904 5'-COOH 2'-(C6H4-4-CI) 2-F 4-NH2
1.905 δ'-COOH 2'-(C6H4-4-CI) 2-CI 4-COOH
1.906 δ'-COOH 2'-(C6H4-4-CI) 2-CN 4-CONH2
1.907 δ'-COOH 2'-(C6H4-4-CI) 2-CH3 4-CSNH2
1.908 δ'-COOH 2'-(C6H4-4-CI) 2-CF3 4-NHCONH2
1.909 δ'-COOH 2'-(C6H4-4-Cl) 2-OCF3 4-NHCSNH2
1.910 δ'-COOH 2'-(C6H4-4-CI) 2-SCF3 4-OCSNH2 1.911 δ'-COOH 2'-(C6H3-2,4-CI2) H H
1.912 δ'-COOH 2'-(C6H3-2,4-CI2) 4-F H
1.913 δ'-COOH 2'-(C6H3-2,4-CI2) 4-CI H
1.914 δ'-COOH 2'-(C6H3-2,4-CI2) 4-CN H
1.915 δ'-COOH 2'-(C6H3-2,4-Cl2) 4-CH3 H
1.916 δ'-COOH 2'-(C6H3-2,4-CI2) 4-CF3 H
1.917 δ'-COOH 2'-(C6H3-2,4-CI2) 4-OCF3 H
1.918 5'-COOH 2'-(C6H3-2,4-CI2) 4-SCF3 H
1.919 5'-COOH 2'-(C6H3-2,4-CI2) 4-S(0)CF3 H
1.920 δ'-COOH 2'-(C6H3-2,4-CI2) 4-S(0)2CF3 H
1.921 δ'-COOH 2'-(C6H3-2,4-Cl2) 2-F H
1.922 5'-COOH 2'-(C6H3-2,4-CI2) 2-CI H
1.923 5'-COOH 2'-(C6H3-2,4-CI2) 2-CN H
1.924 5'-COOH 2'-(C6H3-2,4-CI2) 2-CH3 H
1.925 δ'-COOH 2'-(C6H3-2,4-C(2) 2-CF3 H
1.926 δ'-COOH 2'-(C6H3-2,4-CI2) 2-OCF3 H
1.927 5'-COOH 2'-(C6H3-2,4-CI2) 2-SCF3 H
1.928 δ'-COOH 2'-(C6H3-2,4-CI2) 2-S(0)CF3 H
1.929 δ'-COOH 2'-(C6H3-2,4-CI2) 2-S(0)2CF3 H
1.930 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-NH2
1.931 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-COOH
1.932 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-CONH2
1.933 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-CSNH2
1.934 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-NHCONH2
1.935 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-NHCSNH2
1.936 δ'-COOH 2'-(C6H3-2,4-CI2) H 4-OCSNH2
1.937 δ'-COOH 2'-(C6H3-2,4-CI2) H 3-OC(F2)0-4
1.938 δ'-COOH 2'-(C6H3-2,4-Cl2) H 3-SC(F2)S-4
1.939 δ'-COOH 2'-(C6H3-2,4-CI2) 2-F 4-NH2
1.940 5'-COOH 2'-(C6H3-2,4-CI2) 2-CI 4-COOH
1.941 5'-COOH 2'-(C6H3-2,4-CI2) 2-CN 4-CONH2
1.942 5'-COOH 2'-(C6H3-2,4-CI2) 2-CH3 4-CSNH2
1.943 5'-COOH 2'-(C6H3-2,4-CI2) 2-CF3 4-NHCONH2
1.944 5'-COOH 2'-(C6H3-2,4-CI2) 2-OCF3 4-NHCSNH2 1.945 δ'-COOH 2'-(C6H3-2,4-CI2) 2-SCF3 4-OCSNH2
1.946 δ'-CONH2 H H H
1.947 δ'-CONH2 H 4-F H
1.948 δ'-CONH2 H 4-CI H
1.949 δ'-CONH2 H 4-CN H
1.950 δ'-CONH2 H 4-CH3 H
1.951 5'-CONH2 H 4-CF3 H
1.952 5'-CONH2 H 4-OCF3 H
1.953 δ'-CONH2 H 4-SCF3 H
1.954 δ'-CONH2 H 4-S(0)CF3 H
1.956 δ'-CONH2 H 4-S(0)2CF3 H
1.956 δ'-CONH2 H 2-F H
1.957 δ'-CONH2 H 2-CI H
1.958 δ'-CONH2 H 2-CN H
1.959 δ'-CONH2 H 2-CH3 H
1.960 δ'-CONH2 H 2-CF3 H
1.961 δ'-CONH2 H 2-OCF3 H
1.962 5'-CONH2 H 2-SCF3 H
1.963 δ'-CONH2 H 2-S(0)CF3 H
1.964 5'-CONH2 H 2-S(0)2CF3 H
1.965 5'-CONH2 H H 4-NH2
1.966 δ'-CONH2 H H 4-COOH
1.967 δ'-CONH2 H H 4-CONH2
1.968 δ'-CONH2 H H 4-CSNH2
1.969 5'-CONH2 H H 4-NHCONH2
1.970 5'-CONH2 H H 4-NHCSNH2
1.971 δ'-CONH2 H H 4-OCSNH2
1.972 δ'-CONH2 H H 3-OC(F2)0-4
1.973 δ'-CONH2 H H 3-SC(F2)S-4
1.974 δ'-CONH2 H 2-F 4-NH2
1.976 δ'-CONH2 H 2-CI 4-COOH
1.976 δ'-CONH2 H 2-CN 4-CONH2
1.977 δ'-CONH2 H 2-CH3 4-CSNH2
1.978 5'-CONH2 H 2-CF3 4-NHCONH2 1.979 5'-CONH2 H 2-OCF3 4-NHCSNH2
1.980 δ'-CONH2 H 2-SCF3 4-OCSNH2
1.981 δ'-CONH2 2'-CN H H
1.982 δ'-CONH2 2'-CN 4-F H
1.983 δ'-CONH2 2'-CN 4-CI H
1.984 δ'-CONH2 2'-CN 4-CN H
1.985 δ'-CONH2 2'-CN 4-CH3 H
1.986 δ'-CONH2 2'-CN 4-CF3 H
1.987 δ'-CONH2 2'-CN 4-OCF3 H
1.988 5'-CONH2 2'-CN 4-SCF3 H
1.989 5'-CONH2 2'-CN 4-S(0)CF3 H
1.990 δ'-CONH2 2'-CN 4-S(0)2CF3 H
1.991 5'-CONH2 2'-CN 2-F H
1.992 5'-CONH2 2'-CN 2-CI H
1.993 δ'-CONH2 2'-CN 2-CN H
1.994 δ'-CONH2 2'-CN 2-CH3 H
1.995 δ'-CONH2 2'-CN 2-CF3 H
1.996 δ'-CONH2 2'-CN 2-OCF3 H
1.997 δ'-CONH2 2'-CN 2-SCF3 H
1.998 5'-CONH2 2'-CN 2-S(0)CF3 H
1.999 5'-CONH2 2'-CN 2-S(0)2CF3 H
1.1000 5'-CONH2 2'-CN H 4-NH2
1.1001 5'-CONH2 2'-CN H 4-COOH
1.1002 5'-CONH2 2'-CN H 4-CONH2
1.1003 δ'-CONH2 2'-CN H 4-CSNH2
1.1004 δ'-CONH2 2'-CN H 4-NHCONH2
1.1005 δ'-CONH2 2'-CN H 4-NHCSNH2
1.1006 5'-CONH2 2'-CN H 4-OCSNH2
1.1007 δ'-CONH2 2'-CN H 3-OC(F2)0-4
1.1008 δ'-CONH2 2'-CN H 3-SC(F2)S-4
1.1009 δ'-CONH2 2'-CN 2-F 4-NH2
1.1010 5'-CONH2 2'-CN 2-CI 4-COOH
1.1011 5'-CONH2 2'-CN 2-CN 4-CONH2
1.1012 5'-CONH2 2'-CN 2-CH3 4-CSNH2 1.1013 5'-CONH2 2'-CN 2-CFg 4-NHCONH2
1.1014 5'-CONH2 2'-CN 2-OCF3 4-NHCSNH2
1.1015 5'-CONH2 2'-CN 2-SCF3 4-OCSNH2
1.1016 δ'-CONH2 2'-CH3 H H
1.1017 5'-CONH2 2'-CH3 4-F H
1.1018 5'-CONH2 2'-CH3 4-CI H
1.1019 5'-CONH2 2'-CH3 4-CN H
1.1020 5'-CONH2 2'-CH3 4-CH3 H
1.1021 5'-CONH2 2'-CH3 4-CF3 H
1.1022 5'-CONH2 2'-CH3 4-OCF3 H
1.1023 δ'-CONH2 2'-CH3 4-SCF3 H
1.1024 δ'-CONH2 2'-CH3 4-S(0)CF3 H
1.1025 δ'-CONH2 2'-CH3 4-S(0)2CF3 H
1.1026 δ'-CONH2 2'-CH3 2-F H
1.1027 5'-CONH2 2'-CH3 2-CI H
1.1028 5'-CONH2 2'-CH3 2-CN H
1.1029 δ'-CONH2 2'-CH3 2-CH3 H
1.1030 δ'-CONH2 2'-CH3 2-CF3 H
1.1031 δ'-CONH2 2'-CH3 2-OCF3 H
1.1032 5'-CONH2 2'-CH3 2-SCF3 H
1.1033 5'-CONH2 2'-CH3 2-S(0)CF3 H
1.1034 5'-CONH2 2'-CH3 2-S(0)2CF3 H
1.1035 5'-CONH2 2'-CH3 H 4-NH2
1.1036 5'-CONH2 2'-CH3 H 4-COOH
1.1037 5'-CONH2 2'-CH3 H 4-CONH2
1.1038 5'-CONH2 2'-CH3 H 4-CSNH2
1.1039 δ'-CONH2 2'-CH3 H 4-NHCONH2
1.1040 5'-CONH2 2'-CH3 H 4-NHCSNH2
1.1041 δ'-CONH2 2'-CH3 H 4-OCSNH2
1.1042 5'-CONH2 2'-CH3 H 3-OC(F2)0-4
1.1043 5'-CONH2 2'-CH3 H 3-SC(F2)S-4
1.1044 δ'-CONH2 2'-CH3 2-F 4-NH2
1.1045 δ'-CONH2 2'-CH3 2-CI 4-COOH
1.1046 5'-CONH2 2'-CH3 2-CN 4-CONH2 1.1047 5'-CONH2 2'-CH3 2-CH3 4-CSNH2
1.1048 δ'-CONH2 2'-CH3 2-CF3 4-NHCONH2
1.1049 δ'-CONH2 2'-CH3 2-OCF3 4-NHCSNH2
1.1050 5'-CONH2 2'-CH3 2-SCF3 4-OCSNH2
1.1051 5'-CONH2 2'-CF3 H H
1.1052 5'-CONH2 2'-CF3 4-F H
1.1053 5'-CONH2 2'-CF3 4-CI H
1.1054 5'-CONH2 2'-CF3 4-CN H
1.1055 5'-CONH2 2'-CF3 4-CH3 H
1.1056 5'-CONH2 2'-CF3 4-CF3 H
1.1057 δ'-CONH2 2'-CF3 4-OCF3 H m.p. 169-73°
1.1058 δ'-CONH2 2'-CF3 4-SCF3 H m.p. 161-5°
1.1059 δ'-CONH2 2'-CF3 4-S(0)CF3 H
1.1060 δ'-CONH2 2'-CF3 4-S(0)2CF3 H
1.1061 δ'-CONH2 2'-CF3 2-F H
1.1062 δ'-CONH2 2'-CF3 2-CI H
1.1063 5'-CONH2 2'-CF3 2-CN H
1.1064 5'-CONH2 2'-CF3 2-CH3 H
1.1065 5'-CONH2 2'-CF3 2-CF3 H
1.1066 5'-CONH2 2'-CF3 2-OCF3 H
1.1067 5'-CONH2 2'-CF3 2-SCF3 H
1.1068 5'-CONH2 2'-CF3 2-S(0)CF3 H
1.1069 5'-CONH2 2'-CF3 2-S(0)2CF3 H
1.1070 5'-CONH2 2'-CF3 H 4-NH2
1.1071 5'-CONH2 2'-CF3 H 4-COOH
1.1072 δ'-CONH2 2'-CF3 H 4-CONH2
1.1073 δ'-CONH2 2'-CF3 H 4-CSNH2
1.1074 δ'-CONH2 2'-CF3 H 4-NHCONH2
1.1075 5'-CONH2 2'-CF3 H 4-NHCSNH2
1.1076 5'-CONH2 2'-CF3 H 4-OCSNH2
1.1077 5'-CONH2 2'-CF3 H 3-OC(F2)0-4
1.1078 δ'-CONH2 2'-CF3 H 3-SC(F2)S-4
1.1079 5'-CONH2 2'-CF3 2-F 4-NH2
1.1080 5'-CONH2 2'-CF3 2-CI 4-COOH 1.1081 5'-CONH2 2'-CF3 2-CN 4-CONH2
1.1082 5'-CONH2 2'-CF3 2-CH3 4-CSNH2
1.1083 5'-CONH2 2'-CF3 2-CF3 4-NHCONH2
1.1084 δ'-CONH2 2'-CF3 2-OCF3 4-NHCSNH2
1.1085 δ'-CONH2 2'-CF3 2-SCF3 4-OCSNH2
1.1086 5'-CONH2 2'-OCF3 H H
1.1087 5'-CONH2 2'-OCF3 4-F H
1.1088 5'-CONH2 2'-OCF3 4-CI H
1.1089 5'-CONH2 2'-OCF3 4-CN H
1.1090 5'-CONH2 2'-OCF3 4-CH3 H
1.1091 5'-CONH2 2'-OCF3 4-CF3 H
1.1092 5'-CONH2 2'-OCF3 4-OCF3 H
1.1093 δ'-CONH2 2'-OCF3 4-SCF3 H
1 .1094 5'-CONH2 2'-OCF3 4-S(0)CF3 H
1.1095 5'-CONH2 2'-OCF3 4-S(0)2CF3 H
1.1096 5'-CONH2 2'-OCF3 2-F H
1.1097 δ'-CONH2 2'-OCF3 2-CI H
1.1098 δ'-CONH2 2'-OCF3 2-CN H
1.1099 5'-CONH2 2'-OCF3 2-CH3 H
1.1100 5'-CONH2 2'-OCF3 2-CF3 H
1.1 101 5'-CONH2 2'-OCF3 2-OCF3 H
1.1102 5'-CONH2 2'-OCF3 2-SCF3 H
1.1103 5'-CONH2 2'-OCF3 2-S(0)CF3 H
1.1104 5'-CONH2 2'-OCF3 2-S(0)2CF3 H
1.1105 δ'-CONH2 2'-OCF3 H 4-NH2
1.1106 δ'-CONH2 2'-OCF3 H 4-COOH
1.1107 δ'-CONH2 2'-OCF3 H 4-CONH2
1.1108 5'-CONH2 2'-OCF3 H 4-CSNH2
1 .1109 5'-CONH2 2'-OCF3 H 4-NHCONH2
1.1110 5'-CONH2 2'-OCF3 H 4-NHCSNH2
1.11 11 5'-CONH2 2'-OCF3 H 4-OCSNH2
1.11 12 5'-CONH2 2'-OCF3 H 3-OC(F2)0-4
1.11 13 5'-CONH2 2'-OCF3 H 3-SC(F2)S-4
1.11 14 5'-CONH2 2'-OCF3 2-F 4-NH2 1.1115 5'-CONH2 2'-OCF3 2-CI 4-COOH
1.1116 δ'-CONH2 2'-OCF3 2-CN 4-CONH2
1.1117 δ'-CONH2 2'-OCF3 2-CH3 4-CSNH2
1.1118 δ'-CONH2 2'-OCF3 2-CF3 4-NHCONH2
1.1119 δ'-CONH2 2'-OCF3 2-OCF3 4-NHCSNH2
1.1120 δ'-CONH2 2'-OCF3 2-SCF3 4-OCSNH2
1.1121 δ'-CONH2 2'-C6H5 H H
1.1122 5'-CONH2 2'-C6H5 4-F H
1.1123 5'-CONH2 2'-C6H5 4-CI H
1.1124 5'-CONH2 2'-C6H5 4-CN H
1.1125 5'-CONH2 2'-C6H5 4-CH3 H
1.1126 δ'-CONH2 2'-C6H5 4-CF3 H
1.1127 δ'-CONH2 2'-C8H5 4-OCF3 H
1.1128 5'-CONH2 2'-C6H5 4-SCF3 H
1.1129 5*-CONH2 2'-CeH5 4-S(0)CF3 H
1.1130 δ'-CONH2 2'-C6H5 4-S(0)2CF3 H
1.1131 δ'-CONH2 2'-C6H5 2-F H
1.1132 δ'-CONH2 2'-C6H5 2-CI H
1.1133 δ'-CONH2 2'-C6H5 2-CN H
1.1134 δ'-CONH2 2'-C6H5 2-CH3 H
1.1135 δ'-CONH2 2'-C6H5 2-CF3 H
1.1136 δ'-CONH2 2'-C6H5 2-OCFg H
1.1137 δ'-CONH2 2'-C6H5 2-SCF3 H
1.1138 δ'-CONH2 2'-C8H5 2-S(0)CF3 H
1.1139 δ'-CONH2 2'-C6H5 2-S(0)2CF3 H
1.1140 δ'-CONH2 2'-C6H5 H 4-NH2
1.1141 δ'-CONH2 2'-C6H5 H 4-COOH
1.1142 δ'-CONH2 2'-CeH5 H 4-CONH2
1.1143 δ'-CONH2 2'-C6H5 H 4-CSNH2
1.1144 δ'-CONH2 2'-C6H5 H 4-NHCONH2
1.1145 5'-CONH2 2'-CeH5 H 4-NHCSNH2
1.1146 6'-CONH2 2'-C6H5 H 4-OCSNH2
1.1147 δ'-CONH2 2'-C6H5 H 3-OC(F2)0-4
1.1148 δ'-CONH2 2'-C6H5 H 3-SC(F2)S-4 1.1149 5'-CONH2 2'-C6H5 2-F 4-NH2
1.1160 5'-CONH2 2'-C6H5 2-CI 4-COOH
1.1151 5'-CONH2 2'-C6H5 2-CN 4-CONH2
1.1152 5'-CONH2 2'-C6H5 2-CH3 4-CSNH2
1.1153 5'-CONH2 2'-C6H5 2-CF3 4-NHCONH2
1.1164 5'-CONH2 2'-C6H5 2-OCF3 4-NHCSNH2
1.1 165 5'-CONH2 2'-C6H5 2-SCF3 4-OCSNH2
1.1166 5'-CONH2 2'-(C6H4-4-Ci; H H
1.1157 5'-CONH2 2'~(C6H4-4-CI 4-F H
1.1158 5'-CONH2 2'-(C6H4-4-CP > 4-CI H
1.1159 5'-CONH2 2'-(C6H4-4-CI 4-CN H
1.1160 5'-CONH2 2'-(C6H4-4-Ci; 4-CH3 H
1.1161 5'-CONH2 2'-(C6H4-4-CI) 4-CF3 H
1.1162 5'-CONH2 2'-(C6H4-4-CI] 4-OCFg H
1.1163 5'-CONH2 2'-(C6H4-4-CI) 4-SCF3 H
1.1164 5'-CONH2 2'-(C6H4-4-CI) 4-S(0)CF3 H
1.1165 5'-CONH2 2'-(C6H4-4-CI 4-S(0)2CF3 H
1.1166 5'-CONH2 2'-(C6H4-4-CI] 2-F H
1.1167 5'-CONH2 2'-(C6H4-4-CI) 2-CI H
1.1168 5'-CONH2 2'-(C6H4-4-CI 2-CN H
1.1169 5'-CONH2 2'-(C6H4-4-CI) 2-CH3 H
1.1170 5'-CONH2 2'-(C6H4-4-Ci; 2-CF3 H
1.1171 5'-CONH2 2'-(C6H4-4-CI) 2-OCF3 H
1.1172 5'-CONH2 2'-(C6H4-4-CI] 2-SCF3 H
1.1173 5'-CONH2 2'~(C6H4-4-CI] 2-S(0)CF3 H
1.1174 5'-CONH2 2'-(C6H4-4-CI] 2-S(0)2CF3 H
1.1175 5'-CONH2 2'-(C6H4-4-Ci; H 4-NH2
1.1176 5'-CONH2 2'-(C6H4-4-Ci; H 4-COOH
1.1177 5'-CONH2 2'-(C6H4-4-Ci; H 4-CONH2
1.1178 5'-CONH2 2'-(C6H4-4-Cr H 4-CSNH2
1.1179 5'-CONH2 2'-(C6H4-4-Cl H 4-NHCONH2
1.1180 5'-CONH2 2'-(C6H4-4-CI H 4-NHCSNH2
1.1181 5'-CONH2 2'-(C6H4-4-CI I H 4-OCSNH2
1.1182 5'-CONH2 2'-(C6H4-4-Cl H 3-OC(F2)0-4 1.1183 5'-CONH2 2'-(C6H4-4-CI) H 3-SC(F2)S-4
1.1184 δ'-CONH2 2'-(C6H4-4-CI) 2-F 4-NH2
1.1185 6'-CONH2 2'-(C6H4-4-CI) 2-CI 4-COOH
1.1186 δ'-CONH2 2'-(C6H4-4-CI) 2-CN 4-CONH2
1.1187 δ'-CONH2 2'-(C6H4-4-CI) 2-CH3 4-CSNH2
1.1 188 δ'-CONH2 2'-(C6H4-4-CI) 2-CF3 4-NHCONH2
1.1189 δ'-CONH2 2'-(C6H4-4-CI) 2-OCF3 4-NHCSNH2
1.1190 δ'-CONH2 2'-(C6H4-4-CI) 2-SCF3 4-OCSNH2
1.1191 δ'-CONH2 2'-(C6H3-2,4-CI:/ ) H H
1.1192 δ'-CONH2 2'-(C6H3-2A~C\2' > 4-F H
1.1193 δ'-CONH2 2'-(C6H3-2,4-CI2 4-CI H
1.1194 δ'-CONH2 2'-(C6H3-2,4-CI2 ) 4-CN H
1.1195 δ'-CONH2 2'-(C6H3-2,4-CI2 ) 4-CH3 H
1.1196 δ'-CONH2 2'-(C6H3-2,4-CI2 ) 4-CF3 H
1.1197 5'-CONH2 2'-(C6H3-2,4-CI2 ) 4-OCF3 H
1.1198 δ'-CONH2 2'-(C6H3-2,4-CI2 4-SCF3 H
1.1199 δ'-CONH2 2'-(C6H3-2,4-CI2 4-S(0)CF3 H
1.1200 δ'-CONH2 ^-(CeH^^-CI,1 4-S(0)2CF3 H
1.1201 δ'-CONH2 2'-(C6H3-2,4-CI2 2-F H
1.1202 δ'-CONH2 ^-(dH^^-CI^ 2-CI H
1.1203 δ'-CONH2 2'-(C6H3-2,4-CI2; I 2-CN H
1.1204 5'-CONH2 2'-(C6H3-2,4-CI2 2-CH3 H
1.1205 5'-CONH2 ^-(dH^^-CI; 2-CF3 H
1.1206 δ'-CONH2 2'-(C6H3-2,4-CI2; 2-OCF3 H
1.1207 δ'-CONH2 2'-(C6H3-2,4-Cl2 , 2-SCF3 H
1.1208 δ'-CONH2 2'-(C6H3-2,4-CI2; 2-S(0)CF3 H
1.1209 δ'-CONH2 2'-(C6H3-2,4-Cl2; 2-S(0)2CF3 H
1.1210 5'-CONH2 2'-(C6H3-2,4-CI2 H 4-NH2
1.1211 δ'-CONH2 2'-(C6H3-2,4-CI2 H 4-COOH
1.1212 δ'-CONH2 2'-(C6H3-2,4-CI2 1 H 4-CONH2
1.1213 5'-CONH2 2'-(C6H3-2,4-CI2 H 4-CSNH2
1.1214 5'-CONH2 2'-(C6H3-2,4-CI2 H 4-NHCONH2
1.1215 5'-CONH2 2'-(C6H3-2,4-Cl2 > H 4-NHCSNH2
1.1216 5'-CONH2 2'-(C6H3-2,4-CI2 ) H 4-OCSNH2 1.1217 5'-CONH2 2'-(C6H3-2,4-CI2) H 3-OC(F2)0-4
1.1218 5'-CONH2 2'-(C6H3-2,4-CI2) H 3-SC(F2)S-4
1.1219 5'-CONH2 2'-(C6H3-2,4-CI2) 2-F 4-NH2
1.1220 5'-CONH2 2'-(C6H3-2,4-CI2) 2-CI 4-COOH
1.1221 5'-CONH2 2'-(C6H3-2,4-CI2) 2-CN 4-CONH2
1.1222 5'-CONH2 2'-(C6H3-2,4-CI2) 2-CH3 4-CSNH2
1.1223 5'-CONH2 2'-(C6H3-2,4-Cl2) 2-CF3 4-NHCONH2
1.1224 5'-CONH2 2'-(C6H3-2,4-CI2) 2-OCF3 4-NHCSNH2
1.1225 5'-CONH2 2'-(C6H3-2,4-CI2) 2-SCF3 4-OCSNH2
1.1226 δ'-CONH2 2'-OC6H5 H H
1.1227 δ'-CONH2 2'-OC6H5 4-F H
1.1228 δ'-CONH2 2'-OC6Hs 4-CI H
1.1229 δ'-CONH2 2'-OC6H5 4-CN H
1.1230 δ'-CONH2 2'-OC6H5 4-CH3 H
1.1231 5'-CONH2 2'-OC6H5 4-CF3 H
1.1232 δ'-CONH2 2'-OC6H5 4-OCF3 H
1.1233 δ'-CONH2 2'-OC6H5 4-SCF3 H
1.1234 δ'-CONH2 2'-OC6H5 4-S(0)CF3 H
1.1235 5'-CONH2 2'-OC6H5 4-S(0)2CF3 H
1.1236 5'-CONH2 2'-OC6H5 2-F H
1.1237 5'-CONH2 2'-OC6H5 2-CI H
1.1238 5'-CONH2 2'-OC6H5 2-CN H
1.1239 δ'-CONH2 2'-OC6H5 2-CH3 H
1.1240 δ'-CONH2 2'-OC6Hs 2-CF3 H
1.1241 δ'-CONH2 2'-OC6H5 2-OCF3 H
1.1242 δ'-CONH2 2'-OC6H5 2-SCF3 H
1.1243 δ'-CONH2 2'-OC6H5 2-S(0)CF3 H
1.1244 δ'-CONH2 2'-OC6H5 2-S(0)2CF3 H
1.1245 δ'-CONH2 2'-OC6H5 H 4-NH2
1.1246 5'-CONH2 2'-OC6H5 H 4-COOH
1.1247 5'-CONH2 2'-OC6H5 H 4-CONH2
1.1248 δ'-CONH2 2'-OC6H5 H 4-CSNH2
1.1249 δ'-CONH2 2'-OC6H5 H 4-NHCONH2
1.1250 δ'-CONH2 2'-OC6H5 H 4-NHCSNH2 1.1261 5'-CONH2 2'-OC6H5 H 4-OCSNH2
1.1262 5'-CONH2 2'-OC6H5 H 3-OC(F2)0-4
1.1263 5'-CONH2 2'-OC6H5 H 3-SC(F2)S-4
1.1264 5'-CONH2 2'-OC6H5 2-F 4-NH2
1.1255 5'-CONH2 2'-OC6H5 2-CI 4-COOH
1.1256 5'-CONH2 2'-OC6H5 2-CN 4-CONH2
1.1257 5'-CONH2 2'-OC6H5 2-CH3 4-CSNH2
1.1258 5'-CONH2 2'-OC6H5 2-CF3 4-NHCONH2
1.1259 5'-CONH2 2'-OC6H5 2-OCFs 4-NHCSNH2
1.1260 5'-CONH2 2'-OC6H5 2-SCF3 4-OCSNH2
1.1261 δ'-CONH2 2'-(OC6H4-4-CI) H H
1.1262 δ'-CONH2 2'-(OC6H4-4-CI) 4-F H
1.1263 δ'-CONH2 2'-(OC6H4-4-CI) 4-CI H
1.1264 δ'-CONH2 2'-(OC6H4-4-CI) 4-CN H
1.1265 δ'-CONH2 2'-(OC6H4-4-CI) 4-CH3 H
1.1266 δ'-CONH2 2'-(OC6H4-4-CI) 4-CF3 H
1.1267 5'-CONH2 2'-(OC6H4-4-CI) 4-OCF3 H
1.1268 5'-CONH2 2'-(OC6H4-4-CI) 4-SCF3 H
1.1269 5'-CONH2 2'-(OC6H4-4-CI) 4-S(0)CF3 H
1.1270 5'-CONH2 2'-(OC6H4-4-Cl) 4-S(0)2CF3 H
1.1271 5'-CONH2 2'-(OC6H4-4-CI) 2-F H
1.1272 5'-CONH2 2'-(OC6H4-4-CI) 2-CI H
1.1273 5'-CONH2 2'-(OC6H4-4-CI) 2-CN H
1.1274 5'-CONH2 2'-(OC6H4-4-CI) 2-CH3 H
1.1275 δ'-CONH2 2'-(OC6H4-4-CI) 2-CF3 H
1.1276 δ'-CONH2 2'-(OC6H4-4-CI) 2-OCF3 H
1.1277 δ'-CONH2 2'-(OC6H4-4-CI) 2-SCF3 H
1.1278 δ'-CONH2 2'-(OC6H4-4-CI) 2-S(0)CF3 H
1.1279 5'-CONH2 2'-(OC6H4-4-CI) 2-S(0)2CF3 H
1.1280 5'-CONH2 2'-(OC6H4-4-CI) H 4-NH2
1.1281 δ'-CONH2 2'-(OC6H4-4-CI) H 4-COOH
1.1282 δ'-CONH2 2'-(OC6H4-4-CI) H 4-CONH2
1.1283 5'-CONH2 2'-(OC6H4-4-Cl) H 4-CSNH2
1.1284 δ'-CONH2 2'-(OC6H4-4-Cl) H 4-NHCONH2 1.1285 5'-CONH2 2'-(OC6H4-4-CI) H 4-NHCSNH2
1.1286 δ'-CONH2 2'-(OC6H4-4-CI) H 4-OCSNH2
1.1287 δ'-CONH2 2'-(OC6H4-4-CI) H 3-OC(F2)0-4
1.1288 5'-CONH2 2'-(OC6H4-4-CI) H 3-SC(F2)S-4
1.1289 5'-CONH2 2'-(OC6H4-4-CI) 2-F 4-NH2
1.1290 5'-CONH2 2'-(OC6H4-4-CI) 2-CI 4-COOH
1.1291 δ'-CONH2 2'-(OC6H4-4-Cl) 2-CN 4-CONH2
1.1292 δ'-CONH2 2'-(OC6H4-4-Cl) 2-CH3 4-CSNH2
1.1293 δ'-CONH2 2'-(OC6H4-4-CI) 2-CF3 4-NHCONH2
1.1294 5'-CONH2 2'-(OC6H4-4-CI) 2-OCF3 4-NHCSNH2
1.1295 δ'-CONH2 2'-(OC6H4-4-Cl) 2-SCF3 4-OCSNH2
1.1296 δ'-CONH2 2'-(OC6H3-2,4-Cl2 ) H H
1.1297 δ'-CONH2 2'-(OC6H3-2,4-CI2 I 4-F H
1.1298 5'-CONH2 2'-(OC6H3-2,4-CI2 ) 4-CI H
1.1299 5'-CONH2 2'-(OC6H3-2,4-CI2 ) 4-CN H
1.1300 δ'-CONH2 2'-(OC6H3-2,4-CI2 4-CH3 H
1.1301 5'-CONH2 2'-(OC6H3-2,4-CI2 4-CF3 H
1.1302 5'-CONH2 2'-(OC6H3-2,4-CI2 4-OCF3 H
1.1303 5'-CONH2 2'-(OC6H3-2,4-CI2 4-SCF3 H
1.1304 δ'-CONH2 2'-(OC6H3-2,4-Cl2 , 4-S(0)CF3 H
1.1305 δ'-CONH2 2'-(OC6H3-2,4-Cl2; 4-S(0)2CF3 H
1.1306 δ'-CONH2 2'-(OC6H3-2,4-CI2 2-F H
1.1307 δ'-CONH2 ^-(OCeHa^-CI^ 2-CI H
1.1308 δ'-CONH2 2'-(OC6H3-2,4-CI2; 2-CN H
1.1309 δ'-CONH2 2'-(OC6H3-2,4-CI2^ ) 2-CH3 H
1.1310 δ'-CONH2 2'-(OC6H3-2,4-CI2; 2-CF3 H
1.1311 δ'-CONH2 2'-(OC6H3-2,4-CI2 ) 2-OCF3 H
1.1312 5'-CONH2 2'-(OC6H3-2,4-CI2 ) 2-SCF3 H
1.1313 δ'-CONH2 2'-(OC6H3-2,4-CI2 2-S(0)CF3 H
1.1314 δ'-CONH2 2'-(OC6H3-2,4-CI2 ) 2-S(0)2CF3 H
1.1315 6'-CONH2 2'-(OC6H3-2,4-CI2 ) H 4-NH2
1.1316 δ'-CONH2 2'-(OC6H3-2,4-CI2 ) H 4-COOH
1.1317 δ'-CONH2 2'-(OC6H3-2,4-CI2 ) H 4-CONH2
1.1318 δ'-CONH2 2'-(OC6H3-2,4-CI2 ) H 4-CSNH2 1.1319 5'-CONH2 2'-(OC6H3-2,4-CI2) H 4-NHCONH2
1.1320 5'-CONH2 2'-(OC6H3-2,4-Cl2) H 4-NHCSNH2
1.1321 5'-CONH2 2'-(OC6H3-2,4-CI2) H 4-OCSNH2
1.1322 5'-CONH2 2'-(OC6H3-2,4-CI2) H 3-OC(F2)0-4
1.1323 5'-CONH2 2'-(OC6H3-2,4-CI2) H 3-SC(F2)S-4
1.1324 5'-CONH2 2'-(OC6H3-2,4-CI2) 2-F 4-NH2
1.1325 5'-CONH2 2'-(OC6H3-2,4-CI2) 2-CI 4-COOH
1.1326 6'-CONH2 2'-(OC6H3-2,4-CI2) 2-CN 4-CONH2
1.1327 5'-CONH2 2'-(OC6H3-2,4-CI2) 2-CH3 4-CSNH2
1.1328 δ'-CONH2 2'-(OC6H3-2,4-CI2) 2-CF3 4-NHCONH2
1.1329 6'-CONH2 2'-(OC6H3-2,4-CI2) 2-OCF3 4-NHCSNH2
1.1330 5'-CONH2 2'-(OC6H3-2,4-CI2) 2-SCF3 4-OCSNH2
Bioloqical examples
1. In vivo test aαainst Trichostronqylus colubriformis and Haemonchus contortus in
Monqolian qerbils (Meriones unquiculatus by peroral administration
Six- to eight-week-old Mongolian gerbils are infected, using manufactured feed, with in each case approximately 2 000 larvae of the 3rd stage of T. colubriformis and H. contortus. Six days after infecting, the gerbils are lightly anaesthetized with N20 and are treated by peroral administration with the test compounds, dissolved in a mixture of 2 parts of DMSO and 1 part of polyethylene glycol (PEG 300), with amounts of 100, 32 and 10 - 0.1 mg/kg. On day 9 (3 days after treating), when most of the H. contortus larvae still existing are in the late 4th stage and most of the T. colubriformis are immature adults, the gerbils are sacrificed in order to count the worms. The activity is calculated in % reduction in the number of worms in each gerbil by comparison with the geometric mean of the number of worms from 8 infected and untreated gerbils.
In this test, a large decrease in the nematode infestation is obtained with compounds of the formula I, in particular from Table 1. Namely, compounds 1.392 and 1.1058 reduced the number of nematode worms by more than 95%.
The following test methods can be employed in investigating the insecticidal and/or acaricidal action of the compounds of the formula I on animals and plants.
2. Action against Li. larvae of Lucilia sericata 1 ml of an aqueous suspension of the active substance to be tested is thus mixed at approximately 50°C with 3 ml of a special medium for raising larvae, so that a homogenate with an active ingredient content of either 250 or 125 ppm is formed. Approximately 30 Lucilia larvae (L,) are introduced into each test tube sample. After 4 days, the mortality rate is determined.
3. Acaricidal action against Boophilus microplus (Biarra strain)
An adhesive tape is attached horizontally to a PVC plate such that 10 female Boophilus microplus ticks (Biarra strain) which have sucked themselves full of blood can be adhesively attached to the tape via their backs in a row, next to one another. Each tick is injected, using an injection needle, with 1 μl of a liquid which is a 1 :1 mixture of polyethylene glycol and acetone and in which a certain amount of active ingredient of alternatively 1 , 0.1 or 0.01 μg per tick is dissolved. Control animals receive an injection not comprising an active ingredient. After the treatment, the animals are kept in an insectarium under standard conditions at approximately 28°C and 80% relative humidity until egg laying has occurred and the larvae have hatched from the eggs of the control animals. The activity of a test substance is determined using the IRg0) i.e. that dose of active ingredient is ascertained at which, after 30 days, 9 out of 10 female ticks (= 90%) lay eggs which are not able to hatch.
4. In vitro activity against fed Boophilus microplus females (Biarra):
4 x 10 fed female ticks of the OP-resistant Biarra strain are attached to an adhesive tape and are covered for 1 h with a wad of cotton wool which has been impregnated with an emulsion or suspension of the test compound in concentrations in each case of 500, 125, 31 and 8 ppm. The mortality, egg laying and larval hatching are evaluated 28 days later.
An indication of the activity of the test compounds is the number of the females which
- quickly die, before laying eggs,
- survive for some time, without laying eggs,
- lay eggs in which no embryos develop,
- lay eggs in which embryos develop but from which no larvae hatch, and
- lay eggs in which embryos develop and from which larvae hatch normally in 26 to 27 days.
5. In vitro activity against nymphs of Amblvomma hebraeum
About 5 hungry nymphs are placed in a polystyrene test tube comprising 2 ml of the test compound in solution, suspension or emulsion. After immersing for 10 minutes and shaking for 2 x 10 seconds on a vortex mixer, the test tubes are plugged with a thick wad of cotton wool and are inverted. As soon as all the liquid has been soaked up by the wad of cotton wool, the wad is pushed halfway into the still inverted test tube, so that most of the liquid is squeezed out of the wad of cotton and flows into a Petri dish placed underneath.
The test tubes are now, until evaluation, stored at ambient temperature in a room lit by daylight. After 14 days, the test tubes are immersed in a beaker of boiling water. If, in reaction to the heat, the ticks begin to move, the test substance is inactive at the test concentration; otherwise, the ticks are considered to be dead and the test substance is considered to be active at the test concentration. All substances are tested in a concentration range from 0.1 to 100 ppm.
6. Action against Dermanyssus gallinae
2 to 3 ml of a solution comprising 10 ppm of active ingredient and approximately 200 mites (Dermanyssus gallinae) at various development stages are placed in a glass vessel open at the top. The vessel is subsequently plugged with a wad of cotton wool, shaken for 10 minutes, until the mites have been completely wetted, and then briefly inverted, so that the remaining test solution can be absorbed by the cotton wool. After 3 days, the mortality of the mites is ascertained by counting the dead individuals and is given in per cent.
7. Action against Musca domestica
A sugar cube is treated with a solution of the test substance such that the concentration of test substance in the sugar, after drying overnight, is 250 ppm. This treated cube is placed with a wet wad of cotton wool and 10 adult Musca domestica of an OP-resistant strain on an aluminium dish, is covered with a beaker and is incubated at 25°C. The mortality rate is determined after 24 hours.

Claims

WHAT IS CLAIMED IS:
1. A compound of the formula
Figure imgf000082_0001
wherein
Ar is unsubstituted or one- or poly-substituted aryl or hetaryl;
R-) is hydrogen, C C6alkyl, halo-C C6alkyl, C C6-alkylcarbonyl, C C6alkoxycarbonyl, allyl, C C6alkoxymethyl, unsubstituted or one- or poly-substituted phenylcarbonyl, Cr C6alkylsulfonyl or unsubstituted or one- or poly-substituted phenylsulfonyl;
R2, R3, R , R5 und R6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted Cι-C6alkyl, unsubstituted or one- or poly-substituted C2-C6alkenyl, unsubstituted or one- or poly-substituted C2-C6alkinyl, unsubstituted or one- or poly-substituted d-C6alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, d-C6alkoxy and halo-d- C6alkoxy; unsubstituted or one- or poly-substituted C3-C6cycloalkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen and C C6alkyl; or unsubstituted or one- or poly-substituted phenyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, d-C6alkyl, halo-CrC6alkyl, d-C6alkoxy, halo-d- C6alkoxy, d-C6alkylthio, halo-CrC6alkylthio, C C6alkylsulfinyl, halo-d-C6alkylsulfinyl, C C6alkylsulfonyl, halo-Cι-C6alkylsulfonyl, d-Cβalkylamino and di-Cι-C6alkylamino; or R2 and R3 are together C2-C6alkylene;
R7 and Rio are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, unsubstituted or one- or poly- substituted phenylthiocarbamido, unsubstituted or one- or poly-substituted C C6alkylthiocarbamido, unsubstituted or one- or poly-substituted C C6alkoxythiocarbamido, unsubstituted or one- or poly-substituted phenyloxythiocarbamido, unsubstituted or one- or poly-substituted phenylaminothiocarboxy, unsubstituted or one- or poly-substituted phenyloxythiocarboxy, unsubstituted or one- or poly-substituted phenylaminothiocarboxamido, unsubstituted or one- or poly-substituted C C6alkylaminothiocarbonyl, (C C6-alkyl)2aminothiocarbonyl, phenylaminothiocarbonyl, unsubstituted or one- or poly-substituted phenylsulfanylcarbonyl, unsubstituted or one- or poly-substituted benzylsulfanylcarbonyl, unsubstituted or one- or poly-substituted phenylsulfanyl-C C6alkyl, unsubstituted or one- or poly-substituted phenyl-C C6alkylsulfanyl, C C6alkylsulfanylcarbonyl, d-C6alkylcarbonylsulfanyl, unsubstituted or one- or poly-substituted phenylcarbonylsulfanyl, halo-C2-C6alkynyl, C C6alkylaminothiocarboxy, d-C6alkyloxythiocarboxy, C C6alkylaminothiocarboxamido, (1,3)-oxathiolyl, 2-halo-(1 ,3)- oxathiolyl, (1 ,3)-dioxolyl, 2-halo-(1 ,3)-dioxolyl, sulfonyl, aminosulfonyl, C C6alkylaminosulfonyl, di-C C6alkylaminosulfonyl, unsubstituted or one- or poly-substituted arylaminosulfonyl, unsubstituted or one- or poly-substituted arylsulfonyloxy, unsubstituted or one- or poly-substituted arylsulfonylamino, unsubstituted or one- or poly-substituted aryloxysulfonyl, C C6alkyloxysulfonyl, d-C6alkylaminocarbonylsulfanyl, unsubstituted or one- or poly-substituted phenylaminocarbonylsulfanyl, unsubstituted or one- or poly- substituted phenoxythiocarbonyl, unsubstituted or one- or poly-substituted phenylsulfanylthiocarbonyl, or C C6alkyloxythiocarbonyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of R-i and halogen;
R8 is halogen, nitro, cyano, C C6alkyl, halo-C C6alkyl, C C6alkoxy, halo-C C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloaIkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-C C6alkylthio, CrC6alkylsulfonyloxy, halo-CrC6alkylsulfonyloxy, C C6alkylsulfinyl, halo-C C6alkylsulfinyl, CrC6alkylsuϊfonyl, halo-Cι-C6alkylsulfonyl, C2- C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2- C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C C6alkylamino, di-CrC6alkylamino, C C6alkylsulfonylamino, halo-C C6alkylsulfonylamino, d-C6alkylcarbonyl, halo-C C6alkylcarbonyl, C C6alkoxycarbonyl, C C6alkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly- substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenylmethoximino, unsubstituted or one- or poly-substituted phenylhydroxymethyl, unsubstituted or one- or poly- substituted 1-phenyl-1-hydroxyethyl, unsubstituted or one- or poly-substituted phenylchloromethyl, unsubstituted or one- or poly-substituted phenylcyanomethyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, unsubstituted or one- or poly-substituted phenylacetylenyl, unsubstituted or one- or poly-substituted pyridyloxy, or unsubstituted or one- or poly-substituted phenylsulfanyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of R-! and halogen;
R9 is halogen, nitro, cyano, C C6alkyl, halo-C C6alkyl, d-C6alkoxy, halo-d-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6a!kenyloxy, C C6alkylthio, halo-d-C6alkylthio, Cι-C6alkylsulfonyloxy, halo-CrC6alkylsulfonyloxy, d- C6alkylsulfinyl, halo-C C6alkylsulfinyl, C C6alkylsulfonyl, halo-C C6alkylsulfonyl, C2- C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo-C2-C6alkenylsulfinyl, C2- C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, CrC6alkylamino, di-C C6alkylamino, Cr C6alkylsulfonylamino, halo-d-C6alkylsulfonylamino, CrC6alkylcarbonyl, halo-C C6alkylcarbonyl, d-C6alkoxycarbonyl, d-Cealkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly- substituted arylsulfonyl, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenylmethoximino, unsubstituted or one- or poly- substituted phenylhydroxymethyl, unsubstituted or one- or poly-substituted 1-p-phenyl-1- hydroxyethyl, unsubstituted or one- or poly-substituted phenylchlormethyl, unsubstituted or one- or poly-substituted phenylcyanomethyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, unsubstituted or one- or poly- substituted phenylacetylenyl, unsubstituted or one- or poly-substituted phenoxy, or pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of -\ and halogen; a is , 2, 3 or 4; b is O, 1 , 2, 3 or 4; m, n, o and p are, independent of each other, 0, 1 , 2, 3, 4 or 5;
W is O, S, S(02), N(Rι), C C6alkyl or halo-CrC6alkyl;
Y is O, S or N(Rn); and
Rn is C C6alkyl or unsubstituted or one- or poly-substituted phenyl; with the proviso that m and p are not equal to 0 at the same time.
2. A compound of the formula I according to claim 1 , wherein Ar is unsubstituted or one- or poly-substituted aryl.
3. A compound of the formula I according to claim 1 , wherein Ar is one- or di-substituted aryl.
4. A compound of the formula I according to claim 1 , wherein
RT is hydrogen, C C6alkyl, halo-C C6alkyl, allyl or C C6alkoxymethyl.
5. A compound of the formula I according to claim 1 , wherein Ri is hydrogen, C C4a)kyl or halo-d-C4alkyl.
6. A compound of the formula I according to claim 1, wherein Ri is hydrogen or C C2alkyl.
7. A compound of the formula I according to claim 1 , wherein
R2, R3, R4, R5 und R6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted CrC a!kyl, unsubstituted or one- or poly-substituted C2-C alkenyl, unsubstituted or one- or poly-substituted C2-C4alkinyl or unsubstituted or one- or poly-substituted d-C4alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, d-C6alkoxy and halo- CrC6alkoxy; or R2 and R3 are together C2-C alkylene.
8. A compound of the formula I according to claim 1 , wherein
R2, R3, R4, R5 und R6 are either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted Cι-C4alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C C6alkoxy and halo-C C6alkoxy; or R2 and R3 are together C2-C4alkylene.
9. A compound of the formula I according to claim 1 , wherein
R2, R3, R , R5 und R6 are, independently of one another, hydrogen or halogen.
10. A compound of the formula I according to claim 1 , wherein
R7 and R10 are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (C C6-alkyl)2aminothiocarbonyl, phenylaminothiocarbonyl, C C6alkylsulfanylcarbonyl, d-Cβalkylcarbonylsulfanyl, halo-C2- C6alkynyl, CrC6alkylaminothiocarboxy, d-Cθalkyloxythiocarboxy, C C6alkylaminothiocarboxamido, (1 ,3)-oxathiolyl, 2-halo-(1 ,3)-oxathiolyl, (1 ,3)-dioxolyl, 2-halo- (1,3)-dioxolyl, sulfonyl, aminosulfonyl, CrC6alkylaminosulfonyl, di-C C6alkylaminosulfonyl, CrC6alkyloxysulfonyl, CrC6alkylaminocarbonylsulfanyl, or C C6alkyloxythiocarbonyl; preferably, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2-halo- (1 ,3)-dioxolyl.
11. A compound of the formula I according to claim 1 , wherein R7 and R10 are, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2- halo-(1 ,3)-dioxolyl.
12. A compound of the formula I according to claim 1 , wherein
R7 and R10 are, independently of each other, carboxy or aminocarbonyl.
13. A compound of the formula I according to claim 1 , wherein
R8 is halogen, nitro, cyano, d-C6alkyl, halo-d-C6alkyl, d-C6alkoxy, halo-d-C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-CBcycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-d-C6alkylthio, C2-C6alkenylthio, halo-C2-C6alkenylthio, C C6alkylamino, di- CrC6alkylamino, d-C6alkylcarbonyl, halo-d-C6alkylcarbonyl, d-C6alkoxycarbonyl, C C6alkylaminocarbonyl, di-C C6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, or unsubstituted or one- or poly-substituted pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of RT and halogen.
14. A compound of the formula I according to claim 1 , wherein
Rs is halogen, cyano, CrCδalkyl, halo-d-C6alkyl, Cι-C6alkoxy, halo-C C6alkoxy, unsubstituted or one- or poly-substituted phenyl, or unsubstituted or one- or poly-substituted phenoxy, whereby the substituents in each case can be independent of one another and are halogen.
15. A compound of the formula I according to claim 1 , wherein
R8 is halo-Cι-C6alkyl, or unsubstituted or one- or di-substituted phenoxy, whereby the substituents can be independent of one another and are halogen.
16. A compound of the formula l according to claim 1 , wherein
R9 is halogen, nitro, cyano, C1-C6alkyl, halo-CrC6alkyl, d-C6alkoxy, halo-C C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-CrC6alkylthio, C C6alkylsulfinyl, halo-CrC6alkylsulfinyl, C C6alkylsulfonyl, halo-CrC6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo- C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, Cι-C6alkylcarbonyl, halo-C C6alkylcarbonyl or CrC6alkoxycarbonyl.
17. A compound of the formula I according to claim 1 , wherein
R9 is halogen, cyano, d-C6alkyl, halo-C C6alkyl, d-C6alkoxy, halo-d-C6alkoxy, C3- C6cycloalkylthio, CrC6alkylthio, halo-CrC6alkylthio, C C6alkyIsulfinyl, halo-d-Cealkylsulfinyl, d-C6alkylsulfonyl or halo-C C6alkylsulfonyl.
18. A compound of the formula I according to claim 1 , wherein
R9 is halo-d-C6alkyl, halo-CrC6alkoxy, halo-Cι-C6alkylthio, halo-d-dalkylsulfinyl or halo- C C6alkylsulfonyl.
19. A compound of the formula I according to claim 1 , wherein a is 1 , 2 or 3.
20. A compound of the formula I according to claim 1 , wherein a is 1 or 2.
21. A compound of the formula I according to claim 1 , wherein a is 1.
22. A compound of the formula I according to claim 1 , wherein b is 0, 1 , 2 or 3.
23. A compound of the formula I according to claim 1 , wherein b is 0, 1 or 2.
24. A compound of the formula I according to claim 1 , wherein b is 0.
25. A compound of the formula I according to claim 1 , wherein m, n, o and p are, independent of each other, 0, 1 , 2, 3 or 4, with the proviso that m and p are not equal to 0 at the same time.
26. A compound of the formula I according to claim 1 , wherein m, n, o and p are, independent of each other, 0, 1 , 2 or 3; with the proviso that m and p are not equal to 0 at the same time.
27. A compound of the formula l according to claim 1 , wherein m, n, o and p are, independent of each other, 0, 1 or 2; with the proviso that m and p are not equal to 0 at the same time.
28. A compound of the formula I according to claim 1 , wherein m, n, o and p are, independent of each other, 0 or 1 ; with the proviso that m and p are not equal to 0 at the same time.
29. A compound of the formula l according to claim 1, wherein W is O, S, S(02) or N(Rι).
30. A compound of the formula I according to claim , wherein W is O or S.
31. A compound of the formula I according to claim 1 , wherein W is O.
32. A compound of the formula I according to claim 1 , wherein Y is O or S.
33. A compound of the formula I according to claim 1 , wherein Y is O.
34. A compound of the formula I according to claim , wherein Ar is unsubstituted or one- or poly-substituted aryl;
Ri is hydrogen, d-C6alkyl, halo-C C6alkyl, allyl or C C6alkoxymethyl; R2, R3, R , R5 und R6 are either, independently of one another, hydrogen, halogen, unsubstituted or one- or poly-substituted C C4alkyl, unsubstituted or one- or poly-substituted C2-C4alkenyl, unsubstituted or one- or poly-substituted C2-C alkinyl or unsubstituted or one- or poly-substituted C C alkoxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, C C6alkoxy and halo- C C6alkoxy; or R2 and R3 are together C2-C4alkylene;
R7 and R10 are, independently of each other, NH2, OH, SH, carboxy, aminocarbonyl, aminothiocarbonyl, aminothiocarbonyloxy, ureyl, thioureyl, (Cι-C6-alkyl)2aminothiocarbonyl, phenylaminothiocarbonyl, CrC6alkylsuIfanylcarbonyl, d-C6alkyIcarbonylsulfanyl, halo-C2- C6alkynyl, C C6alkylaminothiocarboxy, d-C6alkyloxythiocarboxy, d- C6alkylaminothiocarboxamido, (1 ,3)-oxathiolyl, 2-halo-(1,3)-oxathiolyl, (1 ,3)-dioxolyl, 2-halo- (1 ,3)-dioxolyl, sulfonyl, aminosulfonyl, Cι-C6alkylaminosulfonyl, di-d-C6alkylaminosulfonyl, CrC6alkyloxysulfonyl, d-C6alkylaminocarbonylsulfanyl, or CrC6alkyloxythiocarbonyl; R8 is halogen, nitro, cyano, C C6alkyl, halo-C C6alkyl, d-C6alkoxy, halo-C C6alkoxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, hato-C2-C6alkenyloxy, Cr C6alkylthio, halo-d-C6alkylthio, C2-C6alkenylthio, halo-C2-C6alkenylthio, d-C6alkylamino, di- C C6alkylamino, C C6alkylcarbonyl, halo-d-C6alkylcarbonyl, d-C6alkoxycarbonyl, d- C6alkylaminocarbonyl, di-CrC6alkylaminocarbonyl, unsubstituted or one- or poly-substituted phenylamino, unsubstituted or one- or poly-substituted phenylcarbonyl, unsubstituted or one- or poly-substituted phenyl, unsubstituted or one- or poly-substituted phenoxy, or unsubstituted or one- or poly-substituted pyridyloxy, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of Ri and halogen;
R9 is halogen, nitro, cyano, C C6alkyl, halo-C1-C6alkyl, Cι-C6alkoxy, halo-CrC6alkσxy, C2-C6alkenyl, halo-C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6cycloalkoxy, C3- C6cycloalkylamino, C3-C6cycloalkylthio, C2-C6alkenyloxy, halo-C2-C6alkenyloxy, C C6alkylthio, halo-C C6alkylthio, CrC6alkylsulfinyl, halo-d-C6alkylsulfinyl, C C6alkylsulfonyl, halo-CrC6alkylsulfonyl, C2-C6alkenylthio, halo-C2-C6alkenylthio, C2-C6alkenylsulfinyl, halo- C2-C6alkenylsulfinyl, C2-C6alkenylsulfonyl, halo-C2-C6alkenylsulfonyl, C C6alkylcarbonyl, halo-Cι-C6alkylcarbonyl or C C6alkoxycarbonyl; a is 1 , 2 or 3; b is 0, 1 , 2 or 3; m, n, o and p are, independent of each other, 0, 1 , 2, 3 or 4;
W is O, S, S(02) or N(Rj); and
Y is O or S; with the proviso that m and p are not equal to 0 at the same time.
35. A compound of the formula I according to claim 1 , wherein Ar is one- or di-substituted aryl;
Ri is hydrogen, d-C4alkyl or halo-d-C4alkyl;
R2, R3, R4, R5 und R6 are either, independently of one another, hydrogen, halogen or unsubstituted or one- or poly-substituted C C alkyl, whereby the substituents in each case can be independent of one another and are chosen from the group consisting of halogen,
Cι-C6alkoxy and halo-CrC6alkoxy; or R2 and R3 are together C2-C4alkylene;
R7 and R10 are, independently of each other, carboxy, aminocarbonyl, (1 ,3)-dioxolyl or 2- halo-(1 ,3)-dioxolyl;
R8 is halogen, cyano, C C6alkyl, halo-C C6alkyl, d-C6alkoxy, halo-CrC6alkoxy, unsubstituted or one- or poly-substituted phenyl, or unsubstituted or one- or poly-substituted phenoxy, whereby the substituents in each case can be independent of one another and are halogen;
R9 is halogen, cyano, CrC6alkyl, halo-d-C6alkyl, d-C6alkoxy, halo-d-C6alkoxy, C3-
C6cycloalkylthio, CrC6alkylthio, halo-C C6alkylthio, Cι-C6alkylsulfinyl, halo-d-C6alkylsulfinyl,
C C6alkylsuιfonyl or halo-CrC6alkylsulfonyl; a is 1 or 2; b is 0, 1 or 2; m, n, o and p are, independent of each other, 0, 1 , 2 or 3;
W is O or S; and
Y is O; with the proviso that m and p are not equal to 0 at the same time.
36. A compound of the formula I according to claim 1 , wherein Ar is one- or di-substituted aryl;
RT is hydrogen or C C2alkyl;
R2> R3. R > 5 und R6 are either, independently of one another, hydrogen or halogen; R7 and R10 are, independently of each other, carboxy or aminocarbonyl;
R8 is halo-d-C6alkyl, or unsubstituted or one- or di-substituted phenoxy, whereby the substituents can be independent of one another and are halogen;
R9 is halo-Cι-C6a)kyl, halo-CrC6alkoxy, halo-CrC6alkylthio, halo-d-C6alkylsulfinyl or halo-
Cι-C6alkylsulfonyl; a is 1 ; b is 0; m, n, o and p are, independent of each other, 0 or 1 ;
W and Y is O; with the proviso that m and p are not equal to 0 at the same time.
37. A compound of the formula I according to claim 1 , with the name 4-[2-cyano-2-(4- trifluoromethoxybenzoylaminσ)-1-propoxy]-3-trifluoromethylbenzamide.
38. A process for the preparation of a compound of the formula I, where Y is O, in each case in the free form or in the salt form, according to claim 1 , which comprises the reaction of a compound of the formula
Figure imgf000090_0001
which is known or can be prepared by analogy to relevant known compounds and in which ι, R∑, 3, R , Rδ> Re, R7> Rs> W, a, b, m and n are as defined above in the formula I, with a compound of the formula
Figure imgf000090_0002
which is known or can be prepared by analogy to relevant known compounds and in which Ar, R9, R10, o and p are as defined above in the formula I and Q is a leaving group, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
39. A process for the preparation of a compound of the formula I, where Y is S, in each case in the free form or in the salt form, according to claim 1 , which comprises the reaction of a compound of the formula I, where Y is O, with a sulfonating agent, preferably P4S10, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
40. A process for the preparation of a compound of the formula I, where Y is NRn, in each case in the free form or in the- salt form, e.g. which comprises the reaction of a compound of the formula I, where Y is S, with a compound of formula NHR^, which is known or can be prepared by analogy to relevant known compounds and in which Rn is as defined above in the formula I, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula I obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula I, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula I obtainable according to the process to a salt or the conversion of a salt of a compound of the formula I obtainable according to the process to the free compound of the formula I or to another salt.
41. A composition for controlling parasites, which comprises, in addition to carriers and/or dispersants, at least one compound of the formula I according to claim 1 as active ingredient.
42. The use of a compound of the formula I according to claim 1 for controlling parasites.
43. A method for controlling parasites, which comprises the use, against the parasites, of an effective amount of at least one compound of the formula I according to claim 1.
44. The use of a compound of the formula l according to claim 1 in a method for controlling parasites in warm-blooded animals.
45. The use of a compound of the formula I according to claim 1 for preparing a pharmaceutical composition against parasites in warm-blooded animals.
PCT/EP2005/006207 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals WO2005121075A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2007526305A JP2008501761A (en) 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use to combat parasites on warm-blooded animals
EP05751761A EP1758849A1 (en) 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals
AU2005251917A AU2005251917B2 (en) 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals
US11/596,961 US7642379B2 (en) 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP04013690.5 2004-06-10
EP04013690 2004-06-10

Publications (1)

Publication Number Publication Date
WO2005121075A1 true WO2005121075A1 (en) 2005-12-22

Family

ID=34925324

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/006207 WO2005121075A1 (en) 2004-06-10 2005-06-09 Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals

Country Status (7)

Country Link
US (1) US7642379B2 (en)
EP (1) EP1758849A1 (en)
JP (1) JP2008501761A (en)
AR (1) AR049391A1 (en)
AU (1) AU2005251917B2 (en)
TW (1) TW200613251A (en)
WO (1) WO2005121075A1 (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008062005A1 (en) * 2006-11-24 2008-05-29 Novartis Ag The use of aminoacetonitril compounds in the control of endoparasites in warm- blood animals.
WO2008102232A1 (en) * 2007-02-21 2008-08-28 Pfizer Limited Benzofuran antiparasitic agents
WO2008144275A1 (en) 2007-05-15 2008-11-27 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
US7608604B2 (en) 2007-02-09 2009-10-27 Pfizer Limited Antiparasitic agents
WO2010056999A1 (en) 2008-11-14 2010-05-20 Merial Limited Enantiomerically enriched aryloazol- 2 -yl cyanoethylamino paraciticidal compounds
US7964621B2 (en) 2008-10-21 2011-06-21 Merial Limited Thioamide compounds, method of making and method of using thereof
US8822689B2 (en) 2012-09-19 2014-09-02 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
US9617285B2 (en) 2013-03-15 2017-04-11 Eli Lilly And Company 1-hydroxy-benzooxaboroles as antiparasitic agents
WO2020112374A1 (en) 2018-11-20 2020-06-04 Boehringer Ingelheim Animal Health USA Inc. Indazolylcyanoethylamino compound, compositions of same, method of making, and methods of using thereof

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0402677D0 (en) * 2003-11-06 2004-03-10 Novartis Ag Organic compounds
NZ714625A (en) * 2012-03-23 2017-02-24 Pitney Pharmaceuticals Pty Ltd Kinase inhibitors for the treatment of cancer
WO2021177334A1 (en) * 2020-03-04 2021-09-10 国立大学法人山口大学 Novel fluoroalkane derivatives and gelling agents using same

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002049641A2 (en) * 2000-12-20 2002-06-27 Novartis Ag Anti-endoparasitic amidoacetonitrils
WO2002060257A1 (en) * 2001-01-22 2002-08-08 Novartis Ag Pharmaceutical composition containing aminoacetonitril compounds and the use thereof for the preparation of a pharmaceutical composition for the treatment of endoparasitic pests in animals
WO2003080577A2 (en) * 2002-03-21 2003-10-02 Novartis Ag Amidoacetonitrile compounds
WO2003097585A2 (en) * 2002-05-22 2003-11-27 Novartis Ag Amidoacetonitrile compounds

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3457294A (en) 1966-04-22 1969-07-22 Abbott Lab N-(substituted-benzoyl) aminoaceto- and aminopropionitriles
GB8530015D0 (en) 1985-12-05 1986-01-15 Ici Plc Biologically active amide derivatives
US6239077B1 (en) * 1998-05-01 2001-05-29 Nihon Nohyaku Co., Ltd. Aminoacetonitrile derivative agricultural and horticultural insecticide containing the same and use thereof
WO2003004474A1 (en) * 2001-07-06 2003-01-16 Syngenta Participations Ag Pesticidally active aminoacetonitriles
TW200400932A (en) 2002-06-19 2004-01-16 Novartis Ag Organic compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002049641A2 (en) * 2000-12-20 2002-06-27 Novartis Ag Anti-endoparasitic amidoacetonitrils
WO2002060257A1 (en) * 2001-01-22 2002-08-08 Novartis Ag Pharmaceutical composition containing aminoacetonitril compounds and the use thereof for the preparation of a pharmaceutical composition for the treatment of endoparasitic pests in animals
WO2003080577A2 (en) * 2002-03-21 2003-10-02 Novartis Ag Amidoacetonitrile compounds
WO2003097585A2 (en) * 2002-05-22 2003-11-27 Novartis Ag Amidoacetonitrile compounds

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008062005A1 (en) * 2006-11-24 2008-05-29 Novartis Ag The use of aminoacetonitril compounds in the control of endoparasites in warm- blood animals.
US7608604B2 (en) 2007-02-09 2009-10-27 Pfizer Limited Antiparasitic agents
JP2010519249A (en) * 2007-02-21 2010-06-03 ファイザー・リミテッド Benzofuran antiparasitic agent
WO2008102232A1 (en) * 2007-02-21 2008-08-28 Pfizer Limited Benzofuran antiparasitic agents
US7622500B2 (en) 2007-02-21 2009-11-24 Pfizer Limited Antiparasitic agents
US8088801B2 (en) 2007-05-15 2012-01-03 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
EP2639228A2 (en) 2007-05-15 2013-09-18 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
EP3428148A1 (en) 2007-05-15 2019-01-16 Merial, Inc. Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
WO2008144275A1 (en) 2007-05-15 2008-11-27 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
US8283475B2 (en) 2007-05-15 2012-10-09 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
EP3088384A1 (en) 2007-05-15 2016-11-02 Merial, Inc. Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
US8314146B2 (en) 2008-10-21 2012-11-20 Merial Limited Thioamide compounds, method of making and method of using thereof
US7964621B2 (en) 2008-10-21 2011-06-21 Merial Limited Thioamide compounds, method of making and method of using thereof
US8461176B2 (en) 2008-11-14 2013-06-11 Merial Limited Enantiomerically enriched aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
WO2010056999A1 (en) 2008-11-14 2010-05-20 Merial Limited Enantiomerically enriched aryloazol- 2 -yl cyanoethylamino paraciticidal compounds
EP3498696A1 (en) 2008-11-14 2019-06-19 Merial, Inc. Enantiomerically enriched aryloazol-2-yl cyanoethylamino parasiticidal compounds
US8822689B2 (en) 2012-09-19 2014-09-02 Merial Limited Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
US9617285B2 (en) 2013-03-15 2017-04-11 Eli Lilly And Company 1-hydroxy-benzooxaboroles as antiparasitic agents
WO2020112374A1 (en) 2018-11-20 2020-06-04 Boehringer Ingelheim Animal Health USA Inc. Indazolylcyanoethylamino compound, compositions of same, method of making, and methods of using thereof

Also Published As

Publication number Publication date
AR049391A1 (en) 2006-07-26
US20080194693A1 (en) 2008-08-14
AU2005251917A1 (en) 2005-12-22
AU2005251917B2 (en) 2009-02-12
TW200613251A (en) 2006-05-01
US7642379B2 (en) 2010-01-05
EP1758849A1 (en) 2007-03-07
JP2008501761A (en) 2008-01-24

Similar Documents

Publication Publication Date Title
CA2544741C (en) Amidoacetonitrile derivatives
US7642379B2 (en) Aminoacetonitrile derivatives and their use for controlling parasites on warm-blooded animals
US20060264653A1 (en) Aminoacetonitrile derivatives and their use for controlling parasites
RU2296119C2 (en) Cyanoacetyl compounds, method for their preparing and their using (variants), composition and method for control of parasites
EP1509221B1 (en) N-acylaminoacetonitrile derivatives and their use for controlling parasites
AU2004299229B2 (en) Amidoacetonitrile derivatives
US7153814B2 (en) Amidoacetonitrile derivatives
WO2003080577A2 (en) Amidoacetonitrile compounds
WO2008062005A1 (en) The use of aminoacetonitril compounds in the control of endoparasites in warm- blood animals.
MXPA04012224A (en) Amidoacetonitrile compounds and their use as pesticides.
RU2284990C2 (en) Derivatives of benzamidoacetonitrile, method for their preparing, composition comprising thereof for nematode control and their using
RU2296747C2 (en) Carbonyloxycyanomethyl compounds, method for their preparing and their using (variants), composition and method for control of parasites
ZA200407974B (en) N-acylaminoacetonitrile derivatives and their use for controlling parasites

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2005751761

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2005251917

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2005251917

Country of ref document: AU

Date of ref document: 20050609

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 2005251917

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 11596961

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2007526305

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

WWP Wipo information: published in national office

Ref document number: 2005751761

Country of ref document: EP